diff --git a/moto/ec2/exceptions.py b/moto/ec2/exceptions.py
index 65f00f132..62f866c0f 100644
--- a/moto/ec2/exceptions.py
+++ b/moto/ec2/exceptions.py
@@ -586,6 +586,14 @@ class InvalidAvailabilityZoneError(EC2ClientError):
         )
 
 
+class AvailabilityZoneNotFromRegionError(EC2ClientError):
+    def __init__(self, availability_zone_value):
+        super().__init__(
+            "InvalidParameterValue",
+            "Invalid Availability Zone ({0})".format(availability_zone_value),
+        )
+
+
 class NetworkAclEntryAlreadyExistsError(EC2ClientError):
     def __init__(self, rule_number):
         super().__init__(
diff --git a/moto/ec2/models/instances.py b/moto/ec2/models/instances.py
index e613c3aa0..f7c93cbf1 100644
--- a/moto/ec2/models/instances.py
+++ b/moto/ec2/models/instances.py
@@ -6,24 +6,28 @@ from datetime import datetime
 from moto.core import get_account_id
 from moto.core import CloudFormationModel
 from moto.core.utils import camelcase_to_underscores
+from moto.ec2.models.instance_types import INSTANCE_TYPE_OFFERINGS
 from moto.packages.boto.ec2.blockdevicemapping import BlockDeviceMapping
-from moto.packages.boto.ec2.instance import Instance as BotoInstance, Reservation
+from moto.packages.boto.ec2.instance import Instance as BotoInstance
+from moto.packages.boto.ec2.instance import Reservation
+
 from ..exceptions import (
+    AvailabilityZoneNotFromRegionError,
     EC2ClientError,
     InvalidInstanceIdError,
     InvalidParameterValueErrorUnknownAttribute,
     OperationNotPermitted4,
 )
-from .core import TaggedEC2Resource
 from ..utils import (
+    convert_tag_spec,
+    filter_reservations,
     random_eni_attach_id,
     random_instance_id,
     random_private_ip,
     random_reservation_id,
-    filter_reservations,
     utc_date_and_time,
-    convert_tag_spec,
 )
+from .core import TaggedEC2Resource
 
 
 class InstanceState(object):
@@ -538,6 +542,15 @@ class InstanceBackend(object):
         raise InvalidInstanceIdError(instance_id)
 
     def add_instances(self, image_id, count, user_data, security_group_names, **kwargs):
+        location_type = "availability-zone" if kwargs.get("placement") else "region"
+        valid_instance_types = INSTANCE_TYPE_OFFERINGS[location_type]
+        if "region_name" in kwargs and kwargs.get("placement"):
+            valid_availability_zones = {
+                instance["Location"]
+                for instance in valid_instance_types[kwargs["region_name"]]
+            }
+            if kwargs["placement"] not in valid_availability_zones:
+                raise AvailabilityZoneNotFromRegionError(kwargs["placement"])
         new_reservation = Reservation()
         new_reservation.id = random_reservation_id()
 
diff --git a/tests/test_ec2/test_instances.py b/tests/test_ec2/test_instances.py
index 77b16cb5e..a2f1e0ab2 100644
--- a/tests/test_ec2/test_instances.py
+++ b/tests/test_ec2/test_instances.py
@@ -1162,6 +1162,24 @@ def test_run_instance_with_placement():
     instance.placement.should.have.key("AvailabilityZone").equal("us-east-1b")
 
 
+@mock_ec2
+def test_run_instance_with_availability_zone_not_from_region():
+    ec2 = boto3.resource("ec2", region_name="us-east-1")
+    with pytest.raises(ClientError) as ex:
+        ec2.create_instances(
+            ImageId=EXAMPLE_AMI_ID,
+            InstanceType="t2.nano",
+            MinCount=1,
+            MaxCount=1,
+            Placement={"AvailabilityZone": "us-west-1b"},
+        )
+
+    ex.value.response["ResponseMetadata"]["HTTPStatusCode"].should.equal(400)
+    ex.value.response["Error"]["Message"].should.equal(
+        "Invalid Availability Zone (us-west-1b)"
+    )
+
+
 @mock_ec2
 def test_run_instance_with_subnet():
     client = boto3.client("ec2", region_name="eu-central-1")