CASE DESCRIPTION: A 7-year-old Siberian Husky-type dog with heterochromia irides was evaluated because of signs of pain associated with the right eye. CLINICAL FINDINGS: Unilateral panuveitis, iris bombé, and secondary glaucoma were detected in the right eye. Tear production was low bilaterally. Facial and truncal poliosis and vitiligo were also evident; skin biopsy specimens were obtained from the nasal planum. Uveodermatologic syndrome was diagnosed on the basis of histopathologic findings of a lichenoid interface dermatitis and pigmentary incontinence within the dermis. Immunohistochemical analysis was performed on skin samples retrospectively, and findings were inconclusive. TREATMENT AND OUTCOME: Treatment involved topical (ocular) and oral administration of corticosteroids, oral administration of azathioprine, and topical (ocular) administration of a carbonic anhydrase inhibitor and a lacrimostimulant. The secondary glaucoma was refractory to treatment, and the right eye was enucleated. Uveodermatologic syndrome was confirmed via histologic examination of ocular tissues. The left eye remained free of inflammation 16 months after the initial diagnosis. The periocular skin and skin of the nose partially regained pigment, but the hair did not. CLINICAL RELEVANCE: Some breeds in which uveodermatologic syndrome has been reported (eg, Siberian Huskies, Old English Sheepdogs, Australian Shepherds, and Shetland Sheepdogs) often have heterochromia irides. This case highlights the fact that dogs with asymmetric uveal pigmentation may have unilateral ocular changes; therefore, uveodermatologic syndrome should not be excluded as a differential diagnosis on the basis of unilateral clinical signs.