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Much of the current understanding of colorectal cancer stems from the study of rare, inherited colorectal cancer syndromes. Mutations in the bone morphogenetic protein (BMP) pathway have been found in juvenile polyposis, an inherited polyposis syndrome that predisposes to colorectal cancer. The hamartomas that develop in these patients and in BMP pathway mutant mice have a remarkable mesenchymal component. Further evidence in mice suggests a primary role for mesenchymal loss of BMP signalling in hamartoma development. Here, we examine this evidence and question its relevance to sporadic colorectal carcinogenesis.