Leukoencephalomyelopathy (LEM) is suggested to be an age-related degenerative condition in geriatric Eastern quolls (Dasyurus viverrinus), manifesting in animals greater than 3.5 yr of age. This case series describes four LEM cases from two zoologic collections; three in nongeriatric animals, with one only 1 yr of age, and details advanced diagnostic investigation, including magnetic resonance imaging, cerebrospinal fluid analysis, and electrodiagnostic studies, not previously reported in Eastern quolls. Animals presented clinically with forelimb proprioceptive deficits and hindlimb and lumbar muscle hypotrophy, which were not noted in previous reports, in addition to hindlimb ataxia. Blindness and emaciation, which have been reported previously, were not seen. Disease progression was variable, and time from first clinical signs to euthanasia ranged from 46 days to over 2 yr. Histopathologic findings in the central nervous system were typical of those in previous LEM cases; concomitant polyneuropathy was observed in two quolls. Our findings suggest that age-related degeneration may not be the only cause of LEM in Eastern quolls. Because all quolls were related, a familial component cannot be excluded. LEM should be further investigated for its potential impact on future captive breeding programs, and our findings suggest that daily quality-of-life assessment should guide euthanasia of affected animals.