Canine lymphoma, as the most common hematopoietic malignancy, encompasses a group of heterogeneous diseases and even within the T-cell immunophenotype, differences in clinical presentation and responses to treatment exist. The aim of this retrospective study was to determine outcomes and prognostic factors of 107 dogs with multicentric non-indolent T-cell lymphoma receiving lomustine based (70%) and non-lomustine based (30%) treatment. The majority were Labradors, Boxers, mixed-breed dogs and Dogue de Bordeaux. Eighty-six percent were substage b, 77% had mediastinal involvement, 15% had suspected bone marrow involvement and 12% had other extra-nodal sites of disease. The overall response rate to induction therapy was 80%; dogs receiving procarbazine in the induction protocol (P = .042), dogs with neutrophil concentration below 8.7x10e9/L (P = 0.006) and mitotic rate below 10 per 5 hpf (P = 0.013), had greater response rates. Median progression-free survival (PFS) for the first remission was 105 days; lack of expression of CD3 on flow cytometry (P < 0.0001) and pretreatment with steroid (P = 0.012) were significantly associated with shorter PFS. Median overall survival (OST) was 136 days; co-expression of CD79a (P = 0.002), lack of CD3 expression on flow cytometry, presence of anemia (P = 0.007) and monocytopenia (P = 0.002) were predictive of shorter OST. Multicentric non-indolent T-cell lymphoma in dogs is an aggressive cancer with new possible prognostic factors. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.