Mouth-related neoplastic and non-neoplastic lesions are commonly found in dogs and cats, and their diagnosis and classification are important for treatment planning and prognosis. This retrospective study analyzed mouth-related lesions in dogs and cats between 2000-2019 from the animal pathology laboratory of the Universidad de Antioquia, Medellín, Colombia. A total of 640 mouth-related lesions affecting 572 dogs (89.4%) and 68 cats (10.6%) were reviewed. Lesions were classified as neoplastic or non-neoplastic. The average age for neoplastic lesions was 8.6 years in dogs and 6.4 years in cats, while for non-neoplastic lesions the average age was 7.7 years for dogs and 5 years for cats. Data was analyzed using descriptive statistical methods according to year and source of report, demographic information for the animal, location of the lesion, and diagnosis. Tissue origin and behavior were variables considered for neoplastic lesions. Melanoma was the most common neoplasia in dogs and squamous cell carcinoma was most common in cats. The most frequent non-neoplastic lesion in dogs was gingival hyperplasia, while in cats the inflammatory lesions showed a wide range of morphological diagnoses. This study described many pathological lesions affecting the oral cavity for both dogs and cats and provides useful epidemiological data for both pathologists and clinicians.