Café au lait macule (CALM) is a well-defined, evenly pigmented brown macule or patch with the characteristic homogeneous color of "coffee with milk" that may be light to dark brown depending on the patient's normal skin pigmentation.

Onset is usually evident in early childhood as a solitary lesion, although it may be present at birth. A single lesion is present in 10%-20% of the US population, and 1% of healthy young adults have up to 3 CALMs. CALMs are located anywhere on the body, although they typically appear on the trunk or lower extremities and rarely on the face. They increase proportionally in size as a child grows and may vary in size (from 1 cm to larger than 20 cm), but they are usually 2-5 cm in adults and are asymptomatic.

Multiple CALMs should alert the clinician to the possibility of an underlying syndrome. Many disorders are associated with multiple CALMs.

Strongly associated syndromes include:

• Neurofibromatosis 
• Multiple familial café au lait syndrome – autosomal dominant
• Legius syndrome – SPRED1 mutation
• McCune-Albright syndrome
• Constitutional mismatch repair deficiency syndrome – mutations in MLH1, MSH2, MSH6, PMS2
• Ring chromosome syndromes – intellectual disability, skeletal anomalies
• LEOPARD / multiple lentigines syndrome – PTPN11 mutation
• Cowden syndrome – PTEN mutation
• Bannayan-Riley-Ruvalcaba syndrome – PTEN mutation

Syndromes that are weakly associated with CALMs include:

• Ataxia-telangiectasia syndrome
• Bloom syndrome
• Fanconi anemia
• Russell-Silver syndrome
• Tuberous sclerosis
• Turner syndrome
• Noonan syndrome
• Multiple endocrine neoplasia syndromes (MEN1)
• Johanson-Blizzard syndrome
• Microcephalic osteodysplastic primordial dwarfism, type II
• Nijmegen breakage syndrome
• Rubinstein-Taybi syndrome
• Kabuki syndrome