Perianal tumors are common in older male dogs. The usefulness of electrochemotherapy in veterinary oncology has already been demonstrated by clinical studies on different malignancies in companion animals. In a prospective non-randomized study, we evaluated the effectiveness of electrochemotherapy in 5 male dogs with 26 perianal adenocarcinomas and 16 male dogs with 40 benign tumors. After premedication and under general anesthesia, the dogs were treated with intratumoral administration of a chemotherapeutic drug (cisplatin or bleomycin) and exposure of tumors to electric pulses, delivered by two different electroporation protocols (Protocol 1 or Protocol 2). At the end of the observation time (median 14 months), an objective response (OR) was obtained in 62/66 tumors (94%) with 87.9% complete responses (CR). No statistically significant difference in OR rate was observed based on histological type (p = 0.110), previous castration (p = 0.088), chemotherapeutic drug used (p = 0.657), and electroporation protocol (p = 0.337). Tumor size at the beginning of the treatment was the only parameter that influenced the treatment outcome (p = 0.04). No major local or general side-effects were noted. We can conclude that electrochemotherapy is an easy, highly effective, safe and cost-effective local approach for the treatment of primary perianal tumors of dogs, especially hepatoid adenoma and epithelioma