The clinical and pathological concept of thromboangiitis obliterans (TAO, Buerger's disease) is still controversial. While the clinical criteria of TAO are relatively well defined, the etiology is unknown and its diagnosis based on pathology is confusing, since there is no consensus on the precise pathological criteria for TAO. To investigate the morphological features that differentiate TAO from arteriosclerosis obliterans (ASO) or thromboembolism, and to clarify the morphological independence of TAO, we studied 94 amputated specimens of lower extremities, including 31 specimens from patients with a clinical diagnosis of TAO and 31 autopsy specimens as control cases. It was revealed that most of the classic morphological features described by Buerger and others are not helpful when considered independently in the differential diagnosis, except for intact internal elastic lamina. In addition, findings of intimal inflammation, intact media and absence of medial calcification were demonstrated to be common in both TAO and thromboembolism. Statistical analysis in the present study, the most comprehensive thus far, showed that novel findings of onion-like-shaped recanalizing vessels in the occluded arteries, adventitial fibrosis without medial fibrosis, swelling of the endothelium of the vasa vasorum and edema beneath the external elastic lamina were characteristic of TAO and would be helpful in a differential diagnosis. When a combination of these morphological features is present, diagnosis of a presumed overlap of TAO and ASO in the same site of the vessel concerned is possible. Furthermore, comparison of statistical evaluations based on morphological features performed in various diagnostic groups implies that the clinical diagnosis of TAO is currently underestimated because the results of the analysis of morphological features of specimens in which TAO was suspected or specimens selected on the basis of a broad and nonspecific definition of TAO were surprisingly similar to the results in strictly defined TAO cases. Our findings suggest that injury and regeneration of minute vessels such as recanalizing vessels and vasa vasorum play a part in the pathogenesis of TAO.