Hereditary mixed polyposis syndrome (HMPS) frequently leads to colorectal carcinoma. Copy number analyses in the chromosomal region thought to harbour the causal genetic lesion identified a 40 kb duplication — encompassing the 3′ end of the SCG5 gene and the region upstream of the gremlin 1 (GREM1) gene — in affected individuals. Tissue expression analyses indicated that the duplication causes GREM1 to be misexpressed in epithelial cells of colonic crypts. As GREM1 is an antagonist of bone morphogenetic protein (BMP) signalling this might explain the tumorigenic effects of the duplication.