Contrary to the intuitive impression of most pathologists, there are still many areas in laboratory medicine where evidence-based medicine (EBM) principles are not applied. These include aspects of both anatomic and clinical pathology. Some non-EBM practices are perpetuated by clinical "consumers" of laboratory services, because of inadequate education, habit, or over-reliance on empirical factors. Other faulty procedures are pathologist-driven, with similar underpinnings. This overview considers several exemplary problem areas representing non-EBM practices in the hospital laboratory. Such examples include ideas and techniques centering on metastatic malignancies, "targeted" oncological therapy, analysis of surgical margins in the excision of neoplasms, general laboratory testing and data utilization, evaluation of selected coagulation defects, administration of blood products, and analysis of hepatic iron-overload syndromes. The concepts illustrating departures from EBM are discussed for each of those topics.