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.

Carotenemia and carotenoderma is in itself harmless, and does not require treatment. In primary carotenoderma, when the use of high quantities of carotene is discontinued the skin color will return to normal. It may take up to several months, however, for this to happen. Infants with this condition should not be taken off prescribed vitamin supplements unless advised to do so by the child's pediatrician.

As to underlying disorders in secondary carotinemia and carotenoderma, treatment depends wholly on the cause.