RFLP studies have indicated a duplication of DNA sequences at the chromosome 5q22 region and showed a breakpoint cluster between the apc and mcc genes in nonpapillary renal-cell carcinoma (RCC). We have now made a high-density fluorescent microsatellite assay to investigate the allelic status and determine the smallest duplication at this region in 62 sporadic non-papillary RCCs. Duplication at each informative locus was found in 27 cases. Partial duplications in 3 tumors delineated 2 distinct regions. One was found at loci D5S659, D5S1720 and w2005 at chromosome band 5q22; this region partially overlaps with the smallest duplicated region found by previous RFLP analysis. Another small duplication was marked by loci D5S816 and D5S476 at chromosome band 5q31.1 and included the alpha-catenin gene (ctnna1).