Background <p>Cutaneous B-cell lymphoma is extremely rare in dogs; only few cases have been reported in veterinary literature, and its clinicopathological characteristics, biological behavior, and classification remain incompletely characterized.</p> Case presentation <p>A 12-year-old spayed female Shih Tzu presented with extensive, multifocal subcutaneous nodules. Histopathology revealed infiltration of neoplastic lymphoid cells within the dermis and subcutaneous tissue without epidermal involvement. Immunohistochemistry revealed strong positivity for cluster of differentiation (CD)79a and paired box 5 (PAX5), no CD3 expression, strong nuclear expression of multiple myeloma oncogene 1 (MUM-1), and a relatively low Ki-67 labeling index (14.28%), suggesting limited proliferative activity. Flow cytometric analysis confirmed B cell dominance, and polymerase chain reaction for antigen receptor rearrangement (PARR) demonstrated clonal rearrangement of the immunoglobulin heavy chain gene. Cytological evaluation of the liver and spleen did not reveal definitive evidence of lymphoma infiltration, and PARR analysis of the splenic aspirate showed polyclonal lymphoid population, providing no molecular evidence of clonal lymphoid proliferation. Despite treatment with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP)-based chemotherapy, only a transient partial response was observed, followed by rapid disease progression.</p> Conclusion <p>This case report describes a rare multifocal non-epitheliotrophic cutaneous B-cell lymphoma in a dog, characterized by aggressive biological behavior, high proliferative activity, and poor response to conventional chemotherapy. These findings highlight the need for further studies to better define the clinicopathological spectrum and optimal management of canine cutaneous B-cell lymphoma.</p>