Background This is the first case report description, to our knowledge, of a cranial mediastinal mass (suspected thymoma) causing orthostatic hypotension in a dog. Case presentation A Labrador Retriever presented for urethral stent placement during cystoscopy secondary to transitional cell carcinoma diagnosis. During anesthesia, the patient had unexpected severe and poorly-responsive hypotension following a shift in position. Several days later, an intrathoracic mass was discovered, raising concerns that the position of the mass in relation to the great vessels and heart may have been the cause of the hypotension. The patient returned for a second stent placement, and computed tomography of the chest confirmed a cranial mediastinal mass, most suspected to be thymoma based on the results of cytology. The patient was kept in sternal recumbency, but when re-positioning to left lateral recumbency, there was a dramatic blood pressure drop that corrected with a return to sternal positioning. Conclusions To our knowledge, orthostatic hypotension has not been described in relation to thymoma in dogs. Thymomas are rare; however, they may be associated with disease of autonomic dysfunction, such as myasthenia gravis, that may lead to orthostatic hypotension. This has been described within the human literature, and we hypothesize it was present in the currently described case. Concurrently, thymomas may grow to a substantial size and cause direct compression of the intrathoracic vasculature. As such, it should be on the differential list for poorly-responsive hypotension following a shift in body positioning under anesthesia.Published version