A retrospective study of the diagnoses of injuries and deaths in equine in Southern Brazil was conducted between 1978 and 2012. All necropsy protocols and other materials of the Regional Diagnostic Laboratory of the Veterinary School of the Federal University of Pelotas were reviewed. The collected data consisted of 2,026 equine materials, including 514 necropsy protocols of and 1,512 other biologic materials, including the protocols of biopsies, organs, swabs, feces, blood, and skin scrapings. From the resulting 2,026 diagnoses, 467 (23.05%) corresponded to neoplasms and tumor like lesions; 168 (8.29%) to parasitic diseases; 135 (6.66%) to bacterial diseases; 31 (1.53%) to viral diseases; 86 (4.24%) to diseases caused by fungi and oomycetes; 50 (2.47%) to intoxication and poisoning by mycotoxins; 9 (0.44%) to metabolic diseases; 60 (2.96%) to other diseases; and 75 (3.70%) to non-transmittable diseases of the digestive tract. Three hundred twenty cases (15.79%) were classified as diseases of unknown etiology. Other diagnoses accounted for 489 of the total 2,026 cases (24.14%). In 44 (8.56%) of the 514 necropsies and 91 (9.47%) of the 961 biopsies of organs mailed into the laboratory, the diagnoses were inconclusive, totaling 135 (9.15%) of the 1,475 in the category. This study demonstrates the importance of skin lesions in horses, as 31.88% (642) of the biopsies received were lesions on the skin of the animals. The most significant tumors observed were equine sarcoid, at 33.18%, and squamous cell carcinoma, at 7.94%. The most common observed causes of death were leucoenceflomalacia (7.59%), rabies (3.70%) thromboembolism by Strongylus vulgaris (2.33%) and monocytic ehrlichiosis (1.75%). INDEX TERMS: Horses, disease of horses, retrospective study, pathology.