Equine sarcoids (ES) and equine malignant melanoma (EMM) are among the tumors affecting horses diagnosed most frequently. Both cutaneous neoplasms can be a significant cause of economic losses, morbidity and mortality in the animals. The treatment of equine skin cancer can be challenging and established, evidence-based therapies resulting in sustained tumor regression are rare. The pentacyclic, lupane-type triterpenes betulinic acid (BA) and betulin can be isolated from many botanical sources, predominantly from the bark of white birch and plane trees. In addition to various biological properties, they have gained attention mainly due to their anticancer features. Within the framework of the current PhD project, the compounds BA, BA derivative NVX-207, and betulin derivative betulinyl-bis-sulfamate were assessed in various in vitro and in vivo studies for their potential as a topical therapy for ES and EMM. In conclusion, the results generated from cell culture experiments, skin permeation assays and studies in the target species are promising. Further advancement of the investigational medicinal products studied herein could lead to an effective topical and marketable, novel drug which helps to relieve suffering and, consequently, improve the welfare of equine skin cancer patients.