diff --git a/django/http/multipartparser.py b/django/http/multipartparser.py
index 9413a1eabb..edf98f6e49 100644
--- a/django/http/multipartparser.py
+++ b/django/http/multipartparser.py
@@ -199,6 +199,12 @@ class MultiPartParser(object):
                         for chunk in field_stream:
                             if transfer_encoding == 'base64':
                                 # We only special-case base64 transfer encoding
+                                # We should always read base64 streams by multiple of 4
+                                over_bytes = len(chunk) % 4
+                                if over_bytes:
+                                    over_chunk = field_stream.read(4 - over_bytes)
+                                    chunk += over_chunk
+
                                 try:
                                     chunk = base64.b64decode(chunk)
                                 except Exception as e:
diff --git a/tests/regressiontests/file_uploads/tests.py b/tests/regressiontests/file_uploads/tests.py
index 8fa140bc18..45e7342abd 100644
--- a/tests/regressiontests/file_uploads/tests.py
+++ b/tests/regressiontests/file_uploads/tests.py
@@ -74,15 +74,14 @@ class FileUploadTests(TestCase):
 
         self.assertEqual(response.status_code, 200)
 
-    def test_base64_upload(self):
-        test_string = "This data will be transmitted base64-encoded."
+    def _test_base64_upload(self, content):
         payload = client.FakePayload("\r\n".join([
             '--' + client.BOUNDARY,
             'Content-Disposition: form-data; name="file"; filename="test.txt"',
             'Content-Type: application/octet-stream',
             'Content-Transfer-Encoding: base64',
             '',]))
-        payload.write(b"\r\n" + base64.b64encode(force_bytes(test_string)) + b"\r\n")
+        payload.write(b"\r\n" + base64.b64encode(force_bytes(content)) + b"\r\n")
         payload.write('--' + client.BOUNDARY + '--\r\n')
         r = {
             'CONTENT_LENGTH': len(payload),
@@ -94,7 +93,13 @@ class FileUploadTests(TestCase):
         response = self.client.request(**r)
         received = json.loads(response.content.decode('utf-8'))
 
-        self.assertEqual(received['file'], test_string)
+        self.assertEqual(received['file'], content)
+
+    def test_base64_upload(self):
+        self._test_base64_upload("This data will be transmitted base64-encoded.")
+
+    def test_big_base64_upload(self):
+        self._test_base64_upload("Big data" * 68000)  # > 512Kb
 
     def test_unicode_file_name(self):
         tdir = sys_tempfile.mkdtemp()