Naxos disease is a recessive association of arrhythmogenic right ventricular cardiomyopathy (ARVC) with wooly hair and palmoplantar keratoderma or similar skin disorder. The clinical and histopathological spectrum of heart disease, molecular genetics and genotype-phenotype correlation are reviewed in 22 affected families with this cardiocutaneous syndrome reported in the literature from Greece, Italy, India, Ecuador, Israel and Turkey. All patients had the hair and skin phenotype from infancy and developed ARVC by adolescence. Mutations in genes encoding the cell adhesion proteins piakoglobin and desmoplakin that truncate the proteins at the C-terminal domains were identified to underlie this syndrome. A particular mutation in Ecuadorian families that truncates the intermediate filament-binding site of desmoplakin results in a variant of Naxos disease with predominantly left ventricular involvement, early morbidity and clinical overlapping with dilated cardiomyopathy (Carvajal syndrome). A lethal autosomal recessive cardiocutaneous syndrome of Poll Hereford calves has been reported in Australia sharing similarities with the human syndrome reviewed here with respect to hair and cardiac phenotype. The cardiomyopathy in Naxos cardiocutaneous syndromes presents with increased arrhythmogenicity and variable left ventricular involovement and is characterized histologically by myocardial loss with fibrofatty or fibrous replacement at subepicardial and mediomural layers. The clinical heterogeneity and tissue characteristics in this cell-adhesion cardiomyopathy might be mutation specific and leads to consideration that the spectrum of ARVC should be broadened.