Background and Objectives: Palmar creases may become as pale as the surrounding skin in severe anemia. However, its sensitivity for assessing severe anemia is questionable, especially in Indian perspective. The study was conducted to evaluate the value of palmar creases in detecting severe anemia. Materials and Methods: Patients with laboratory confirmed anemia were assessed for pallor of palmar creases without information of patient’s hemoglobin (Hb) value to the observer. Sensitivity and specificity of palmar creases pallor were assessed for severe anemia. Role of clinical signs such as severe pallor of conjunctiva, tongue and nail-beds and pulmonary ejection systolic murmur were also assessed for predicting severe anemia. Results: Of 200 patients, 50 had severe anemia (Hb <7 g/dL). Only six patients with Hb <7 g/dL were found to have creases looking similar pale to surrounding skin. Average Hb level of them was 4.05 ± 0.82 g/dL. No patients with Hb ≥7 g/dL had pale palmar creases. In severely anemic patients, its sensitivity is only 12%, but specificity is 100%, and positive likelihood ratio is >1200. Severe pallor of conjunctiva, tongue and nail-beds and pulmonary ejection systolic murmur were more sensitive, but specificity of them was less for severe anemia. Conclusions: Color of palmar creases is a poorly sensitive indicator of the severe anemia especially in Indians due to the pigmentation of creases. Hence, the absence of palmar crease pallor is not likely to be of use in ruling out severe anemia.