Alveolar soft part sarcoma (ASPS) is a rare malignant neoplasm characterized by slow growth and indolent behavior. The role of proliferative markers and tumor suppressor genes is unknown in these tumors. To investigate their potential role in diagnosis and prognosis, we studied 13 cases of primary ASPS and 14 metastases and correlated them with clinicopathologic parameters. Immunohistochemistry was performed with anti-p53 and anti-Ki-67 antibodies. Polymerase chain reaction after tumor microdissection was performed to search for possible loss of heterozygosity in chromosomes 1p, 9p, 17q, 22q, and TP53 to identify possible changes that may clarify the histogenesis of these tumors. Four of five (80%) primary ASPS cases were positive for Ki-67 and all of them developed later metastases. One patient whose tumor did not stain for Ki-67 remained free of disease for 9 years. Eleven of 13 (85%) metastases were positive for Ki-67; however, there was no correlation with final outcome. All the primary ASPS cases analyzed for p53 yielded negative results, but two (15%) of 13 metastases were weakly positive. There was no correlation of these markers with prognosis or clinicopathologic parameters. No loss of heterozygosity was found except in one of nine (11%) informative metastases for D1S165 (at 1p36). Our preliminary data suggest that Ki-67-positive immunostaining may be a prognostic indicator for the development of metastases in ASPS.