Depressive conditions are common psychiatric disorders with formidable and debilitating consequences. The association of brain lesions with depressive symptoms has been already reported. We describe a case of a patient, in whom a frontal lobe tumor was initially presented with a depressive episode. By discussing the neuropathological framework of depression we present an account of how localized brain lesions could give rise to depressive disorders. A failure in conventional antidepressant treatment might increase the risk of life-threatening consequences such as suicidal ideation. We therefore emphasize the importance of neuroimaging examinations in evaluation of depressive conditions even in the absence of focal neurological signs.