We report an unusual case of a two-year-old girl with metastatic retinoblastoma and massive bone marrow involvement who showed the overt presence of circulating retinoblastoma cells in peripheral blood smears a few days before death. This extended disease developed after an early relapse that followed abandoned primary chemotherapy. To the best of our knowledge, there are no previous reports about the presence of circulating retinoblastoma cells in peripheral blood films. We conclude that the search for bone marrow invasion in patients with disseminated retinoblastoma should be exhaustive to achieve an accurate staging assessment. Peripheral blood smears should be examined cautiously to detect occasional circulating retinoblastoma cells when the bone marrow is massively involved.