Background <p>Oral tumours are common in dogs and cats. When surgery is not an option, medical treatment including chemotherapy, radiotherapy or electrochemotherapy (ECT) can be used. This case report describes an inoperable oral papillary squamous cell carcinoma (OSCC) in a dog treated with ECT and tyrosine kinase inhibitors (TKIs).</p> Case presentation <p>A 12-year and 9-month-old, female neutered crossbreed dog was presented to our institution for further investigations of a large, right-sided oral mass. The patient was initially staged with a CT scan which did not show any evidence of local or distant metastatic disease; cytopathology of the draining lymph nodes was compatible with reactive hyperplasia. An incisional biopsy of the mass was performed, leading to a diagnosis of a moderately differentiated, papillary OSCC, with high mitotic and Ki67 indices. The dog was started on oral firocoxib and imatinib mesylate and subsequently underwent four ECT sessions, showing a complete response. A month after the fourth treatment, a tissue biopsy was repeated and confirmed the presence of residual, disease. Since then, the patient was started on toceranib phosphate. Three months following treatment, the dog’s clinical condition deteriorated, and the owner opted for euthanasia. The survival time was 175&#xa0;days since ECT was started.&#xa0;</p> Conclusions <p>ECT is a feasible treatment for inoperable oral SCC and can be considered in association with TKIs to treat microscopic, residual disease.</p>