The standard of care treatment for localised feline nasal lymphoma (FeNL) is radiation therapy (RT). Early local or systemic failure occurs in 17%-45% of cats treated with RT with or without chemotherapy. The aim of this study was to determine if pre-treatment biopsy characteristics could predict early tumour progression in FeNL. Inclusion criteria consisted of histologically confirmed FeNL, available paraffin blocks of diagnostic quality, localised to the sinonasal cavity on staging pre-RT, treated with IMRT/IGRT (10 × 4.2 Gy) without chemotherapy and at least 1 year follow-up. All pre-RT biopsies were reviewed and evaluated with CD3, CD20, CD79a, pan-CK and Ki-67 immunohistochemistry and the mitotic activity index was determined. The primary endpoint was progression-free survival (PFS) at 1 year and hazard-ratios (HR) with confidence interval (CI) were calculated. Twenty-eight cats fit the inclusion criteria, and all had diffuse large B-cell lymphoma. Seventeen cats (61%) were progression free at 1 year. Of the 11 cats that progressed in the first year, two had local progression, two had both local and systemic progression and seven had systemic progression. The mitotic index (HR: 1.03, CI 0.9-1.19, p = 0.645), Ki-67 (HR: 1.00, CI 0.98-1.02, p = 0.845) and >
30% of tumour-infiltrating T cells (HR: 0.38, CI 0.09-1.56, p = 0.175) were not significantly associated with PFS. In this uniformly RT treated population of FeNL, none of the evaluated pre-RT histologic parameters could predict early treatment failure.