Retinoblastoma, when it kills by metastasis, almost always does so within 5 years of enucleation. The median time to death was 6.4 months in unilateral cases and 14.2 months in bilateral cases. Multivariate statistical analysis of 361 cases of retinoblastoma indicated that histologic detection of invasion of the tumor into the optic nerve or orbit were the risk factors most highly predictive of death from retinoblastoma. Choroidal invasion was not significantly associated with a fatal outcome. Histologic evidence of a cataract, failure to diagnose retinoblastoma clinically, and bilaterality were also significant risk factors. The authors believe that in at least two of the cases of bilateral retinoblastoma death did not result from metastasis to the brain as was originally diagnosed, but resulted from the development of an independent primary intracranial neuroblastic tumor, a syndrome designated "trilateral retinoblastoma."