**1. Introduction**

Canine melanoma is an aggressive tumor that originates from melanocytes in different sites in the animal body, including the oral cavity. Melanoma of the oral cavity is a highly aggressive disease and is the most prevalent cancer in the oral cavity [1–9]. According to the Oncology Pathology Working Group (OPWG) consensus, some of the most common histologic features of melanoma include intracytoplasmic melanin, variable cell morphology, junctional activity, pagetoid growth, presence of neoplastic cells at the mucosal–submucosal junction, and finely stippled to vesiculated nucleus with a prominent central nucleolus ("owl's eye") [9]. Distant metastasis, lymphatic invasion, nuclear atypia, mitotic index, tumor size/volume, and tumor score are also related to poor prognosis [6, 9, 10].

Canine melanoma is an immunogenic tumor, and investigations of different aspects associated with immune cells in tumor development and progression have been reported in the literature [1–10]. Moreover, genomic and transcriptomic data from canine oral melanoma have revealed several pathways associated with inflammatory processes, including T-helper cell differentiation [1]. Thus, evaluation of the immune components of canine melanoma is pivotal for a better understanding of tumor biology and for developing new therapies. Therefore, this chapter reviews the association between the immune system and canine melanoma development, prognosis, and treatment.
