Since loss of heterozygosity (LOH) on the long arm of chromosome 6q is frequently observed in salivary gland carcinomas, we examined 28 salivary gland carcinomas using 24 microsat- ellite markers mapping to 6q15-27 to identify the commonly deleted region that we felt might contain one or more tumor suppressor genes. LOH was detected in at least one locus in 10 of 28 tumors (35.7%). The most frequently deleted regions occurred between D6S1581 and D6S305 (LOH cluster region 1 (LCR1) and between D6S297 and D6S1590 (LCR2). LOH was observed in 60% of adenoid cystic carcinomas (ACC) and in 57.1% of mucoepidermoid carcinomas (MEC), but was not observed in any locus in any other histological subtypes studied. The gene encoding for thrombospondin-2 (TSP-2) is located in LCR2 and 8 of 9 tumors demonstrating LOH in this region also showed significantly decreased TSP-2 expression by immunohistochemistry. As TSP-2 is a potent inhibitor of tumor growth and angiogenesis, we examined whether TSP-2 expression correlated to microvascular angiogenesis in these tumors and discovered that microvessel counts were significantly higher in lesions with decreased TSP-2 expression (P = 0.02). Our results suggest that 6q LOH may be a significant event in salivary gland carcinogenesis, particularly in ACC and MEC, and that the correlated decrease of TSP-2 expression also plays a critical role.