Human colon cancer is rapidly becoming a paradigm in the study of cancer biology. This review explores some of the recent developments in the molecular pathology of this tumor. There major pathogenetic mechanisms are discussed: (1) tumor cell cohesiveness mediated by proteins involved in cell–cell and cell–matrix adhesion; (2) mutations and loss of heterozygosity of tumor suppressor genes, leading to critical steps in the progression to adenoma and carcinoma, as illustrated by the adenomatous polyposis coli gene; and (3) germline mutations in mismatch repair genes causing generalized genetic instability as observed in hereditary nonpolyposis colorectal cancer. The recent advances in molecular biology techniques have enhanced the understanding of the genetic events that occur in tumorigenesis and may now be applied in the development of new diagnostic and treatment strategies.