Objective: Cancer of unknown primary site (CUP) remains a significant oncological problem for the elderly. Chemotherapy is the mainstay of treatment but the ideal regimen remains uncertain. We have performed a retrospective subset analysis of a previously reported prospective phase 2 trial evaluating efficacy and toxicity of the combination of gemcitabine (G) and carboplatin (C) in elderly patients with CUP. Materials and methods: In the original study, 51 patients with CUP, who had ECOG performance status (PS) 0-2, were treated with G 1000mg/m 2 iv days 1 and 8, and C AUC 5 iv day 8 every 3weeks to a maximum of 9 cycles. A subset of patients aged ≥65years were re-analysed for response rate, toxicity, progression-free survival (PFS) and overall survival (OS). These data were subsequently compared with the remaining patients aged <65years. Results: Data for 29 patients aged ≥ 65. years were compared with 22 patients aged < 65. years. For patients ≥ 65 years, response rate (RR) was 38%, median PFS was 20. weeks and median OS was 37. weeks. For patients < 65 years, RR was 14%, median PFS was 11. weeks and median OS was 33. weeks. The differences in PFS and OS were not statistically significant. Significant toxicity (predominantly myelosuppression) was recorded in 45% of patients ≥ 65 years and 32% in patients < 65 years, but was considered generally manageable for all patients. Conclusions: The GC regimen is active in CUP with excellent tolerability and should be considered for elderly patients with CUP.