To further elucidate the somatic genetic alterations leading to acquired choroidal and ciliochoroidal melanoma, we screened every autosomal arm and the X chromosome of 50 primary posterior melanomas (31 choroidal tumors and 19 ciliochoroidal tumors). A minimum of two microsatellite markers were used to achieve at least 90% informativity (excluding X). Twenty-eight of 47 informative tumors (59%) showed allelic loss of all informative markers on chromosome 3, consistent with monosomy 3 (M3). Allelic imbalance of 8q was observed in 60% of tumors. A total of 28% of tumors displayed allelic loss of 6p. We then compared these genetic alterations with the status of chromosome 3 and found a relative absence of 6p alteration in tumors with M3 (P = 0.0005). Additionally, all observed 8q imbalance was associated with either M3 or alteration of 6p, suggesting that 8q alterations occur later in tumor progression. The mutual exclusivity of M3 and 6p alterations suggests a bifurcated tumor progression model. In this model, M3 or 6p loss identify distinct pathways, both followed by 8q loss in tumor progression.