A potent modifying locus of intestinal tumorigenesis in the mouse was recently identified as secretory phospholipase A2 (sPLA2). The human homologue of sPLA2 maps to chromosome 1p35, a region frequently lost in human tumors. To evaluate the possibility that sPLA2 was a tumor suppressor gene that was the target of the 1p loss events, we identified polymorphisms within the human sPLA2 gene. Using these polymorphisms, 31% of 16 colorectal carcinomas were found to lose a sPLA2 allele. However, sequence analysis of the complete coding region of sPLA2 revealed no somatic mutations in the remaining allele of those tumors with allelic loss, nor in 18 additional colorectal cancers. Thus, sPLA2 is within the chromosomal region often lost during colorectal tumorigenesis, but mutations of this gene do not appear to play a major role in colorectal cancer development, and sPLA2 is unlikely to be the 1p35 tumor suppressor.