Family Pi is a high-risk cancer family in which more than 40% of the members of two generations have had cancer, mostly breast, endometrial, and gastrointestinal. An analysis of over 30 polymorphic genetic markers for possible genetic linkage to a gene increasing susceptibility to cancer revealed positive LOD scores to markers within or near the major histocompatibility complex [HLA-A,B (0.639), properdin B (Bf) (0.162), glyoxylase-1 (GLO-1) (0.166)] as well as to acid phosphatas (0.566) and MNSs (0.449). While no LOD score is statistically significant in the linkage analyses of this family alone, the data are compatible with the hypothesis that a cancer-susceptibility gene(s) (CSG) may be located on chromosome 6p, 2p, or 4q. Analyses of additional families with a similar cancer syndrome are warranted to resolve this ambiquity.