diff --git a/pandas/core/ops.py b/pandas/core/ops.py
index 01df9218c1936..cfd32e9c33c07 100644
--- a/pandas/core/ops.py
+++ b/pandas/core/ops.py
@@ -487,9 +487,9 @@ def _offset(lvalues, rvalues):
 
                 # with tz, convert to UTC
                 if self.is_datetime64tz_lhs:
-                    lvalues = lvalues.tz_localize(None)
+                    lvalues = lvalues.tz_convert('UTC')
                 if self.is_datetime64tz_rhs:
-                    rvalues = rvalues.tz_localize(None)
+                    rvalues = rvalues.tz_convert('UTC')
 
                 lvalues = lvalues.view(np.int64)
                 rvalues = rvalues.view(np.int64)
diff --git a/pandas/tests/series/test_operators.py b/pandas/tests/series/test_operators.py
index d36cc0c303dfe..94c7a8dd7b5d1 100644
--- a/pandas/tests/series/test_operators.py
+++ b/pandas/tests/series/test_operators.py
@@ -1375,3 +1375,18 @@ def test_datetime64_with_index(self):
         df['expected'] = df['date'] - df.index.to_series()
         df['result'] = df['date'] - df.index
         assert_series_equal(df['result'], df['expected'], check_names=False)
+
+    # See gh-12290
+    def test_datetime64_single_non_native(self):
+        f = Series([pd.Timestamp('2016-02-08 13:43:14.605000',
+                                 tz='America/Sao_Paulo')])
+        s = Series([pd.Timestamp('2016-02-10 13:43:14.605000',
+                                 tz='America/Sao_Paulo')])
+
+        out = f - s
+        expected = Series(pd.Timedelta('-2days'))
+        assert_series_equal(out, expected)
+
+        out = s - f
+        expected = Series(pd.Timedelta('2days'))
+        assert_series_equal(out, expected)