Individuals inheriting the same mutation predisposing to cancer may show very different outcomes, ranging from early aggressive cancer to disease-free survival. Experimental mouse models can provide a powerful tool to identify factors in the environment and genetic background that account for such modifications. The Min mouse strain¹, in which the Apc^Min mutation disrupts the mouse homologue of the human familial polyposis gene², develops intestinal neoplasms whose multiplicity is strongly affected by genetic background³. We previously mapped^4,5 a strong modifier locus, Mom1 (modifier of Min-1), to a 4-cM region on mouse chromosome 4 containing a candidate gene Pla2g2a encoding a secretory phospholipase⁶. Here, we report that a cosmid transgene overexpressing Pla2g2a caused a reduction in tumour multiplicity and size, comparable to that conferred by a single copy of the resistance allele of Mom1. These results offer strong evidence that this secretory phospholipase can provide active tumour resistance. The association of Pla2g2a with Mom1 thus withstands a strong functional test and is likely to represent the successful identification of a polymorphic quantitative trait locus in mammals.