Carotenoids are deposited in the intercellular lipids of the stratum corneum, and the color change is most prominent in regions of increased sweating and thickness of this layer. This includes the palms, soles, knees, and nasolabial folds, although the discoloration can be generalized. The primary factor differentiating carotenoderma from jaundice is the characteristic sparing of the sclerae in carotenoderma, which would be involved in jaundice if the bilirubin is at a level to cause skin findings. In contrast to jaundice, carotenoderma is reported to be better observed under artificial light. It is of note that lycopenemia is specifically associated with discoloration of the soft palate and deposition in the liver parenchyma.

Hyperbilirubinemia is the main differential diagnosis to be considered in evaluating jaundice suspected to be carotenemia.

Excessive consumption of lycopene, a plant pigment similar to carotene and present in tomatoes, can cause a deep orange discoloration of the skin. Like carotenodermia, lycopenemia is harmless.

Excessive consumption of elemental silver, silver dust or silver compounds can cause the skin to be colored blue or bluish-grey. This condition is called argyria. A similar skin color can result from prolonged exposure to gold, typically as a little-used medical treatment. The gold-induced greyish skin color is called chrysiasis. Argyria and chrysiasis, however, are irreversible, unlike carotenosis.