PURPOSE: Retinoblastoma is an intraocular tumor occurring almost exclusively in young children. Germline mutations in the Rb1 gene confer hereditary predisposition to retinoblastoma. To identify germline mutations in the Rb1 gene in Korean retinoblastoma patients, we analyzed germline mutations of the Rb1 gene in 4 Korean retinoblastoma patients from 3 families. MATERIALS AND METHODS: All patients were bilaterally affected in early childhood. First patient and second patient were same family members (SNU-RB1-1 and -2), and in the third patient (SNU-RB2), tumor cells had metastasized to the central nervous system 2 years after treatment of retinoblastoma. Fourth patient (SNU-RB3) developed secondary osteosarcoma in the nasal cavity 15 years after treatment of retinoblastoma. We have used PCR-SSCP analysis and DNA sequencing analysis to screen germline mutations. RESULTS: We found one missense mutation in the fourth patient (SNU-RB3). This was a point mutation from AAA (lysine) to GAA (glutamine) at codon 616 in exon 19 of the Rb1 gene. CONCLUSION: We confirmed one germline mutation of the Rb1 gene in one Korean patient who had a sporadic bilateral retinoblastoma and osteosarcoma. Identification of the germline mutation in Rb1 gene would help to improve the presymptomatic diagnosis and clinical management of retinoblastoma patients.