Multiple café au lait spots or macules (CALMs) are associated with a variety of genetic disorders with a range of different manifestations. The most common condition causing CALMs is neurofibromatosis type 1 (NF1), occurring in approximately 1 in 3,000 individuals. The diagnostic criteria for NF1 was initially developed in 1987 and is currently being revised. Early detection of NF1 is important to ensure that patients are referred to the appropriate specialists (e.g., ophthalmology, neuropsychology) and families are provided with education and support. The primary care provider’s recognition of CALMs with appropriate referral to a provider able to diagnose and treat NF1 is essential.