Although a small number of cases of feline diffuse iris melanoma have been documented to metastasize, the prognosis is not known. In this matched observational study, the survival time of 34 cats with enucleation due to histologically confirmed diffuse iris melanoma was recorded. These results are compared to the survival times of 83 age-matched control cats. Affected cats had enucleation between 2 and 10 years prior to the study. One group of control cats with eye disease had enucleation for either lymphoplasmacytic uveitis (27 cases), ocular trauma (seven cases), or endophthalmitis (four cases). In these control cats, enucleations were performed between 2 and 10 years prior to this study. Forty-five additional control cats presented for vaccination between 2 and 10 years prior to the study. The extent of diffuse iris melanoma at the time of enucleation in affected cats was graded according to the extent of involvement of ocular tissues and the invasiveness of the tumor. Affected cats have a significantly decreased survival compared with control cats and cats with extensive tumors at the time of enucleation have the lowest survival rates. Cats with tumors confined to the iris survive at the same rate as controls. These results suggests that early enucleation is important to avoid premature death, presumed to be due to cancer metastasis in cats with diffuse iris melanoma.