diff --git a/doc/source/whatsnew/v1.4.0.rst b/doc/source/whatsnew/v1.4.0.rst
index e42360558d284..9ebacabd7a839 100644
--- a/doc/source/whatsnew/v1.4.0.rst
+++ b/doc/source/whatsnew/v1.4.0.rst
@@ -291,6 +291,7 @@ Styler
 Other
 ^^^^^
 - Bug in :meth:`CustomBusinessMonthBegin.__add__` (:meth:`CustomBusinessMonthEnd.__add__`) not applying the extra ``offset`` parameter when beginning (end) of the target month is already a business day (:issue:`41356`)
+- Bug in :meth:`DataFrame.isin` and :meth:`Series.isin` incorrectly comparing ``None`` values to ``False`` (:issue:`35565`)
 
 .. ***DO NOT USE THIS SECTION***
 
diff --git a/pandas/_libs/ops.pyx b/pandas/_libs/ops.pyx
index ac8a7f2cc57f7..c0ba5b0fcaedf 100644
--- a/pandas/_libs/ops.pyx
+++ b/pandas/_libs/ops.pyx
@@ -157,8 +157,9 @@ def vec_compare(ndarray[object] left, ndarray[object] right, object op) -> ndarr
         for i in range(n):
             x = left[i]
             y = right[i]
-
-            if checknull(x) or checknull(y):
+            if x is None and y is None:
+                result[i] = False
+            elif checknull(x) or checknull(y):
                 result[i] = True
             else:
                 result[i] = PyObject_RichCompareBool(x, y, flag)
@@ -166,8 +167,9 @@ def vec_compare(ndarray[object] left, ndarray[object] right, object op) -> ndarr
         for i in range(n):
             x = left[i]
             y = right[i]
-
-            if checknull(x) or checknull(y):
+            if x is None and y is None:
+                result[i] = True
+            elif checknull(x) or checknull(y):
                 result[i] = False
             else:
                 result[i] = PyObject_RichCompareBool(x, y, flag)
diff --git a/pandas/tests/test_algos.py b/pandas/tests/test_algos.py
index b4836dffffa06..d7bd8ed9ef81a 100644
--- a/pandas/tests/test_algos.py
+++ b/pandas/tests/test_algos.py
@@ -1084,6 +1084,14 @@ def test_isin_float_df_string_search(self):
         expected_false = DataFrame({"values": [False, False]})
         tm.assert_frame_equal(result, expected_false)
 
+    def test_isin_none(self):
+        # GH35565
+        x = DataFrame([["foo", "bar"], [1, None]])
+        y = x[1].copy()
+        res = x.isin(y)
+        expected = DataFrame([[False, True], [False, True]])
+        tm.assert_frame_equal(res, expected)
+
 
 class TestValueCounts:
     def test_value_counts(self):