Literature regarding molecular abnormalities of red blood cells (RBCs) that do not affect cell morphology, function or life span, observed in several non haematological diseases, has been reviewed with the aim of pointing out the pathological conditions in which RBC studies may offer useful biological and/or clinical information. RBC abnormalities have been classified into membrane and cytoplasm alterations; lipid and protein alterations of the membrane have been considered separately. We conclude that RBCs may often provide a simple and reliable tool for investigations concerning the diagnosis and/or treatment of many diseases, even if in some cases the true biological and clinical value of the remarks has to be evaluated further.