['To analyze the clinical characteristics and genetic background associated with the presence of hand arthropathy, as determined by radiological findings, in Italian patients with hereditary hemochromatosis (HHC).', 'In 88 consecutive unselected patients with phenotypically expressed HHC, joint involvement was systematically evaluated in plain radiographs of hands, wrists, lumbar spine, pelvis, and knees. Risk factors considered were age, sex, body mass index, alcohol abuse, organ involvement at other sites, and indices of iron overload, including ferritin, transferrin saturation, and iron removed to reach depletion. HFE genotype was also considered. The independent role of risk factors was tested by logistic regression analysis.', 'Thirty-two subjects (36%) showed signs of metacarpophalangeal (MCP) arthropathy. Intercarpal, radiocarpal, and chondrocalcinosis were less frequent and occurred in association with MCP arthropathy. At multivariate analysis MCP arthropathy was independently associated with older age [odds ratio (OR) 1.20, 95% confidence interval (CI) 1.1-1.33/yr; p = 0.0001], higher ferritin levels at diagnosis (OR 4.17, 95% CI 1.60-13.9 for values > 1000 ng/ml; p = 0.008), the presence of the C282Y +/+ and C282Y/H63D HFE genotypes (OR 2.69, 95% CI 1.09-7.87; p = 0.04), and higher percentage transferrin saturation (OR 1.05, 95% CI 1-1.1; p = 0.05). The severity of arthropathy was independently associated with older age (p = 0.03) and higher ferritin values (p = 0.05).'] Is the hand arthropathy of hereditary hemochromatosis strongly associated with iron overload?