We describe a Caucasian family with asymptomatic, nonconsanguineous parents, and a daughter with unexplained microcytic anemia diagnosed on routine hemoglobin screening at her 12-month well child check. After failed response to oral and parental iron supplementation, iron refractory iron deficiency anemia was suspected. The family underwent genetic testing and the proband was found to be a compound heterozygote for 2 previously unreported TMPRSS6 variants.