diff -u b/modules/simpletest/drupal_web_test_case.php b/modules/simpletest/drupal_web_test_case.php
--- b/modules/simpletest/drupal_web_test_case.php
+++ b/modules/simpletest/drupal_web_test_case.php
@@ -85,6 +85,10 @@
    */
   protected $setup = FALSE;
 
+  protected $setupDatabasePrefix = FALSE;
+
+  protected $setupEnvironment = FALSE;
+
   /**
    * Constructor for DrupalTestCase.
    *
@@ -1284,6 +1288,12 @@
   protected function changeDatabasePrefix() {
     if (empty($this->databasePrefix)) {
       $this->prepareDatabasePrefix();
+      // If $this->prepareDatabasePrefix() failed to work, return without
+      // setting $this->setupDatabasePrefix to TRUE, so setUp() methods will
+      // know to bail out.
+      if (empty($this->databasePrefix)) {
+        return;
+      }
     }
 
     // Clone the current connection and replace the current prefix.
@@ -1295,6 +1305,9 @@
       );
     }
     Database::addConnectionInfo('default', 'default', $connection_info['default']);
+
+    // Indicate the database prefix was set up correctly.
+    $this->setupDatabasePrefix = TRUE;
   }
 
   /**
@@ -1355,6 +1368,9 @@
     $test_info = &$GLOBALS['drupal_test_info'];
     $test_info['test_run_id'] = $this->databasePrefix;
     $test_info['in_child_site'] = FALSE;
+
+    // Indicate the environment was set up correctly.
+    $this->setupEnvironment = TRUE;
   }
 
   /**
@@ -1386,6 +1402,9 @@
 
     // Prepare the environment for running tests.
     $this->prepareEnvironment();
+    if (!$this->setupEnvironment) {
+      return FALSE;
+    }
 
     // Reset all statics and variables to perform tests in a clean environment.
     $conf = array();
@@ -1396,6 +1415,9 @@
     // changed, since DrupalCacheArray implementations attempt to
     // write back to persistent caches when they are destructed.
     $this->changeDatabasePrefix();
+    if (!$this->setupDatabasePrefix) {
+      return FALSE;
+    }
 
     // Preset the 'install_profile' system variable, so the first call into
     // system_rebuild_module_data() (in drupal_install_system()) will register
diff -u b/modules/simpletest/tests/upgrade/upgrade.test b/modules/simpletest/tests/upgrade/upgrade.test
--- b/modules/simpletest/tests/upgrade/upgrade.test
+++ b/modules/simpletest/tests/upgrade/upgrade.test
@@ -102,6 +102,9 @@
 
     // Prepare the environment for running tests.
     $this->prepareEnvironment();
+    if (!$this->setupEnvironment) {
+      return FALSE;
+    }
 
     // Reset all statics and variables to perform tests in a clean environment.
     $conf = array();
@@ -112,6 +115,9 @@
     // changed, since DrupalCacheArray implementations attempt to
     // write back to persistent caches when they are destructed.
     $this->changeDatabasePrefix();
+    if (!$this->setupDatabasePrefix) {
+      return FALSE;
+    }
 
     // Unregister the registry.
     // This is required to make sure that the database layer works properly.