This retrospective study determined disease free survival (DFS) and progression freesurvival (PFS) in chemo-naïve dogs with multicentric or cranial mediastinal high-grade T-celllymphoma, treated with a first-line CCNU-L(-chlorambucil)-CHOP protocol. Of thirteen dogswith multicentric lymphoma, 92.3% achieved a complete remission (CR), and the median DFSand PFS was 317 and 256 days, respectively. Three dogs had cranial mediastinal lymphoma,and achieved a CR with a median DFS and PFS of 978 and 1007 days, respectively. The oneandtwo-year DFS/PFS probability estimate for dogs with multicentric lymphoma was 0.50/0.46and 0.42/0.38, respectively, for dogs with cranial mediastinal lymphoma 0.67/0.67. Neutropeniaand thrombocytopenia were reported in 52.9% and 50% of the dogs, respectively, while 56.3%experienced grade 1-4 nephrotoxicity, hypothesized to be lomustine-induced. It was concludedthat, compared to historical data, the currently described first-line CCNU-L(-chlorambucil)-CHOP protocol could benefit the survival of dogs with multicentric or cranial mediastinal highgradeT-cell lymphoma.