Amyloidosis is the pathologic extracellular deposition of amyloid, a proteinaceous substance, in various tissues and organs. The most common form of amyloidosis in domestic animals is amyloid A amyloidosis, though amyloid light chain, amyloid β, and islet amyloid polypeptide amyloidosis have been documented. In reptiles, amyloidosis, or amyloid-like disorders, are considered rare. This research brief reviews an index case in a California kingsnake (Lampropeltis getula californiae) with amyloid-like deposition in the liver associated with fatal hepatic hematoma formation. In a review of 9,677 snakes in the archives of Northwest ZooPath from 1998 to 2019, 10 other cases (0.001%) of amyloid-like deposition in snakes were found, colubrids were overrepresented (n = 7; 64%), and most cases (n = 6; 54%) were greater than 15 yr of age at postmortem exam. Histologically, the liver was the most commonly affected organ (n = 10; 91%), with the kidney and heart affected less commonly. Amyloid-like material stained lightly positive with Congo red, was slightly positive with the periodic acid–Schiff reaction and did not stain with Masson trichrome stain. Ultrastructurally, amyloid-like material was composed of unbranched 10.27- to 13.20-nm-wide fibrils. Two cases had concurrent neoplasia, and inflammation was noted histologically in seven total cases. Four of the cases had no evidence of concurrent inflammation. The data described here indicate that amyloidosis in reptiles may be an aging change and not necessarily associated with inflammation or other disease processes.