diff --git a/doc/source/whatsnew/v0.15.2.txt b/doc/source/whatsnew/v0.15.2.txt
index 8d6e3cb0512b4..944a78ad3691e 100644
--- a/doc/source/whatsnew/v0.15.2.txt
+++ b/doc/source/whatsnew/v0.15.2.txt
@@ -71,6 +71,7 @@ Bug Fixes
 - ``Timedelta`` kwargs may now be numpy ints and floats (:issue:`8757`).
 - ``sql_schema`` now generates dialect appropriate ``CREATE TABLE`` statements (:issue:`8697`)
 - ``slice`` string method now takes step into account (:issue:`8754`)
+- Bug in ``BlockManager`` where setting values with different type would break block integrity (:issue:`8850`)
 - Fix negative step support for label-based slices (:issue:`8753`)
 
   Old behavior:
diff --git a/pandas/core/internals.py b/pandas/core/internals.py
index 306aebede2476..14c4fb17c2b34 100644
--- a/pandas/core/internals.py
+++ b/pandas/core/internals.py
@@ -2985,7 +2985,7 @@ def value_getitem(placement):
             loc = [loc]
 
         blknos = self._blknos[loc]
-        blklocs = self._blklocs[loc]
+        blklocs = self._blklocs[loc].copy()
 
         unfit_mgr_locs = []
         unfit_val_locs = []
diff --git a/pandas/tests/test_internals.py b/pandas/tests/test_internals.py
index 5bc7558efb471..37b557743b731 100644
--- a/pandas/tests/test_internals.py
+++ b/pandas/tests/test_internals.py
@@ -430,6 +430,17 @@ def test_set_change_dtype(self):
         mgr2.set('quux', randn(N))
         self.assertEqual(mgr2.get('quux').dtype, np.float_)
 
+    def test_set_change_dtype_slice(self): # GH8850
+        cols = MultiIndex.from_tuples([('1st','a'), ('2nd','b'), ('3rd','c')])
+        df = DataFrame([[1.0, 2, 3], [4.0, 5, 6]], columns=cols)
+        df['2nd'] = df['2nd'] * 2.0
+
+        self.assertEqual(sorted(df.blocks.keys()), ['float64', 'int64'])
+        assert_frame_equal(df.blocks['float64'],
+                DataFrame([[1.0, 4.0], [4.0, 10.0]], columns=cols[:2]))
+        assert_frame_equal(df.blocks['int64'],
+                DataFrame([[3], [6]], columns=cols[2:]))
+
     def test_copy(self):
         shallow = self.mgr.copy(deep=False)