diff --git a/pandas/core/frame.py b/pandas/core/frame.py
index 68ea6795d47dd..410e0d7e8aeeb 100644
--- a/pandas/core/frame.py
+++ b/pandas/core/frame.py
@@ -14093,7 +14093,11 @@ def to_period(
         setattr(new_obj, axis_name, new_ax)
         return new_obj
 
-    def isin(self, values: Series | DataFrame | Sequence | Mapping) -> DataFrame:
+    def isin(
+        self,
+        values: Series | DataFrame | Sequence | Mapping,
+        ignore_index: bool = False,
+    ) -> DataFrame:
         """
         Whether each element in the DataFrame is contained in values.
 
@@ -14101,10 +14105,26 @@ def isin(self, values: Series | DataFrame | Sequence | Mapping) -> DataFrame:
         ----------
         values : iterable, Series, DataFrame or dict
             The result will only be true at a location if all the
-            labels match. If `values` is a Series, that's the index. If
-            `values` is a dict, the keys must be the column names,
-            which must match. If `values` is a DataFrame,
-            then both the index and column labels must match.
+            labels match.
+
+            - If `values` is a Series, the index labels must match.
+            - If `values` is a dict, the keys must be column names,
+              which must match.
+            - If `values` is a DataFrame:
+
+              * When ``ignore_index=False`` (default), both the index
+                and column labels must match, and comparison is done
+                elementwise.
+              * When ``ignore_index=True``, only column labels must
+                match. Each element in the DataFrame is compared
+                against the set of values in the corresponding column
+                of ``values``, ignoring row index alignment.
+
+        ignore_index : bool, default False
+            *Only valid when `values` is a DataFrame.*
+            If True, ignore index alignment and simply check
+            if each value in each column occurs in the same
+            column of `values`.
 
         Returns
         -------
@@ -14121,8 +14141,8 @@ def isin(self, values: Series | DataFrame | Sequence | Mapping) -> DataFrame:
 
         Notes
         -----
-            ``__iter__`` is used (and not ``__contains__``) to iterate over values
-            when checking if it contains the elements in DataFrame.
+        ``__iter__`` is used (and not ``__contains__``) to iterate over values
+        when checking if it contains the elements in DataFrame.
 
         Examples
         --------
@@ -14185,9 +14205,12 @@ def isin(self, values: Series | DataFrame | Sequence | Mapping) -> DataFrame:
                 raise ValueError("cannot compute isin with a duplicate axis.")
             result = self.eq(values.reindex_like(self), axis="index")
         elif isinstance(values, DataFrame):
-            if not (values.columns.is_unique and values.index.is_unique):
-                raise ValueError("cannot compute isin with a duplicate axis.")
-            result = self.eq(values.reindex_like(self))
+            if ignore_index:
+                result = self.isin(values.to_dict("list"))
+            else:
+                if not (values.columns.is_unique and values.index.is_unique):
+                    raise ValueError("cannot compute isin with a duplicate axis.")
+                result = self.eq(values.reindex_like(self))
         else:
             if not is_list_like(values):
                 raise TypeError(
diff --git a/pandas/tests/frame/methods/test_isin.py b/pandas/tests/frame/methods/test_isin.py
index b4511aad27a93..83a1353c9a77e 100644
--- a/pandas/tests/frame/methods/test_isin.py
+++ b/pandas/tests/frame/methods/test_isin.py
@@ -225,3 +225,65 @@ def test_isin_not_lossy(self):
         result = df.isin([val])
         expected = DataFrame({"a": [True], "b": [False]})
         tm.assert_frame_equal(result, expected)
+
+    @pytest.mark.parametrize(
+        "values_df,expected",
+        [
+            # Case 1: Same values, different order
+            (
+                DataFrame({"A": [2, 1], "B": [0, 2]}),
+                DataFrame({"A": [True, True], "B": [True, True]}),
+            ),
+            # Case 2: Subset of values
+            (
+                DataFrame({"A": [1], "B": [0]}),
+                DataFrame({"A": [True, False], "B": [True, False]}),
+            ),
+            # Case 3: No matching values
+            (
+                DataFrame({"A": [5, 6], "B": [7, 8]}),
+                DataFrame({"A": [False, False], "B": [False, False]}),
+            ),
+            # Case 4: Missing column
+            pytest.param(
+                DataFrame({"A": [1, 2]}),
+                DataFrame({"A": [True, True], "B": [False, False]}),
+                id="missing_column",
+            ),
+        ],
+    )
+    def test_isin_ignore_index(self, values_df, expected):
+        """
+        Test DataFrame.isin() with ignore_index=True for various scenarios.
+
+        GH#62620
+        """
+        df = DataFrame({"A": [1, 2], "B": [0, 2]})
+        result = df.isin(values_df, ignore_index=True)
+        tm.assert_frame_equal(result, expected)
+
+    def test_isin_ignore_index_with_duplicates(self):
+        """
+        Test that ignore_index=True works correctly with duplicate values.
+
+        GH#62620
+        """
+        df = DataFrame({"A": [1, 2, 3], "B": [0, 0, 0]})
+        values = DataFrame({"A": [1, 1, 2], "B": [0, 0, 0]})
+        result = df.isin(values, ignore_index=True)
+        expected = DataFrame({"A": [True, True, False], "B": [True, True, True]})
+        tm.assert_frame_equal(result, expected)
+
+    def test_isin_ignore_index_diff_indexes(self):
+        """
+        Test that ignore_index=True correctly ignores index values.
+
+        GH#62620
+        """
+        df = DataFrame({"A": [1, 2], "B": [0, 2]}, index=["row1", "row2"])
+        values = DataFrame({"A": [2, 1], "B": [2, 0]}, index=["x", "y"])
+        result = df.isin(values, ignore_index=True)
+        expected = DataFrame(
+            {"A": [True, True], "B": [True, True]}, index=["row1", "row2"]
+        )
+        tm.assert_frame_equal(result, expected)