Our previous cytogenetic and microsatellite analyses showed a terminal deletion of chromosome 3p segments with a breakpoint region between 3p11.2 and 3p14.1 bands in 98% of non-papillary renal cell carcinomas (RCC). This breakpoint region covers approx. 20-25 cM genetic distance. Earlier, we found a higher frequency of rearrangements at chromosome 3p11.2 and have therefore now analyzed 74 sporadic and 26 VHL-associated RCCs with 6 polymorphic microsatellite markers mapped to this region. Thirty-three per cent of the breakpoints were mapped to a genetic distance of less than one-twentieth of the large breakpoint region 3p11.2-14.1. We suggest that unstable DNA sequences at chromosome 3p11.2 serve as a genetic basis for deletions and homologous and non-homologous recombinations to remove distal 3p sequences with one copy of RCC gene(s) in different types of tumors. We have identified a YAC clone 909d5 that spans the most frequently occurring breaks between loci D3S1251, D3S1101, and D3S1552 and allows this region to be cloned.