Permanent significant hyperchromia, equivalent to hyperspherocytosis, the leading symptom of hereditary spherocytosis (HS), has become accessible to routine screening by hematologic automats using double angle laser technology. This has resulted in the discovery of a much higher incidence of this anomaly. In previous investigations we suggested the permanence of significant hyperchromia as obligate criterion for the diagnosis HS. Intercurrent normal percentages of hyperchromic RBC rather pointed to secondary, non-hereditary spherocytosis. Describing 6 typical cases, we demonstrate that occasional normal percentages of hyperchromic red blood cells occurring during phases of anemia and/or iron deficiency are compatible with the diagnosis of HS.