Soft-tissue sarcomas can be divided into translocation-associated (TA) and non-TA sarcomas, the latter of which is often characterized by pleomorphic cytomorphology and aneuploidy. The aberrant expression of MAD2, an essential component of the mitotic spindle checkpoint, has been recently shown to promote aneuploidy. The aim of the present paper was to assess MAD2 status on immunohistochemistry in 50 TA sarcomas with known fusion genes and 50 non-TA pleomorphic sarcomas. MAD2 was overexpressed in 26 TA (52%) and 33 non-TA sarcomas (66%). Notably, the MAD2 overexpression was frequently detected in TA sarcomas with atypical or high-grade morphology, such as round cell liposarcoma and fibrosarcomatous dermatofibrosarcoma protuberans. The MAD2 overexpression was significantly frequent in non-TA sarcomas compared with TA tumors without such atypical or high grade morphology (P = 0.012). In addition, sarcomas with MAD2 overexpression were significantly rich in abnormal mitotic figures, including multipolar mitoses and anaphase bridges, compared to MAD2-negative tumors (P = 0.003), although the overall mitotic activity was equivalent between the sarcomas with or without the MAD2 overexpression. These data suggest that the aberrant MAD2 expression is potentially associated with pleomorphic morphology and abnormal mitosis in soft-tissue sarcomas, as well as with high-grade tumor progression in its TA subset.