Ochronosis is a cutaneous disorder caused by the accumulation of phenols, either endogenously as homogentisic acid in patients with alkaptonuria (autosomal recessive disorder with deficiency of the enzyme homogentisic acid oxidase), or exogenously in patients using phenol products such as topical creams containing hydroquinone or the intramuscular application of antimalarial drugs. Exogenous ochronosis (EO) typically affects the face and was reported in patients with dark skin such as Black South Africans or Hispanics who use skin-lightening products containing hydroquinone for extended periods. Recently more cases have been reported worldwide even in patients with lighter skin tones, to include Eastern Indians, Asians, and Europeans. However, just 39 cases of EO have been reported in the US literature from 1983 to 2020. Here we present two cases; a 69 and a 45-year-old female who were seen for melasma, given hydroquinone 4% cream daily and tretinoin 0.05%. Both patients noticed brown spots on their cheeks, which progressively enlarged and darkened in color. The diagnosis of ochronosis was confirmed by characteristic histopathological features on the punch biopsy. Unfortunately, neither patient responded to multiple treatments (to include, tazarotene 0.1% gel and pimecrolimus ointment, topical corticosteroids, and avoidance of hydroquinone containing products). We also present a case of classic (endogenous) ochronosis in a patient with alkaptonuria to picture the histological similarities of these two entities. EO is an important clinical consideration because early diagnosis and treatment may offer the best outcome for this notoriously refractory clinical diagnosis.