BACKGROUNDAcquired cold urticaria (ACU) is usually a self-limited, sporadic, cutaneous disease diagnosed based on history and a positive cold stimulation time test (CSTT) result. We describe 3 unrelated families (A, B, and C) with lifelong atypical cold urticaria distinguished from ACU and familial cold autoinflammatory syndrome.OBJECTIVEWe sought to describe a new hereditary disease of cold urticaria and study its pathogenesis.METHODSQuestionnaires, interviews, physical examinations, skin testing, and biopsies were performed. Absolute values, means, and prevalence percentages of data are reported.RESULTSThirty-five subjects are described with familial atypical cold urticaria (FACU; family A, 17; family B, 8; and family C, 10) displaying an autosomal dominant pattern of inheritance. All tested subjects had negative CSTT results. Completed questionnaires from affected and unaffected members of families A and B (n = 35) revealed that all affected subjects had lifelong symptoms that began in early childhood with pruritus, erythema, and urticaria after cold exposure. Angioedema (family A, 23%; family B, 42%) and syncope, near syncope, or both (family A, 46%; family B, 86%) were also present. Triggers included cold atmosphere (100%), aquatic activities (family A, 92%; family B, 100%), handling cold objects (family A, 54%; family B, 71%), and ingestion of cold foods or beverages (family A, 69%; family B, 100%). Skin biopsy specimens demonstrated a mast cell infiltrate with the appearance of degranulation after cold challenge.CONCLUSIONSFACU is a new cold-induced inherited disease that is different than ACU in its natural history, atmospheric cold elicitation, severity of systemic reactions, and CSTT results. FACU differs from familial cold autoinflammatory syndrome in symptom timing and the absence of fever, chills, and joint pain. The cause is suspected to be mast cell related. Treatment of reactions is similar to that for ACU. Further evaluation of pathogenesis and genetics is warranted.