This case series presents a 20-year-old Quarter horse gelding and a 10-year-old Thoroughbred gelding with a histologic diagnosis of aggressive submural neoplasia, including an anaplastic sarcoma and a squamous cell carcinoma respectively. The current case series describes these neoplasias with radiography, computed tomography, magnetic resonance imaging and histopathology with immunohistochemistry. The purpose of this case series is to identify the clinical pattern of chronic reoccurring lameness in these cases and highlight the appearance of expansile osteolytic pathology of the distal phalanx with adjacent hoof wall abnormalities. Advanced imaging has the potential to assist with a differential diagnosis list and surgical planning in patients such as these however obtaining a cellular sample for histopathological examination remains necessary for definitive diagnosis.