In some families, individuals carrying the same PTEN mutation have been noted to display very different phenotypes, to the extent of separate diagnoses of Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome.16, 17 Additionally, the spectrum of tumours arising in heterozygous mice carrying a null allele of Pten also appears to be strongly dependent on genetic background.18 Studies of the mutation types (missense vs truncation) and positions (phosphatase vs C2 domain) within PTEN have argued for19 and against2, 20 genotype-phenotype relationships. The gene discussed is PTEN; the disease is Cowden disease.