For more than a century, the accepted wisdom has been that true regeneration is only possible in either very simple or very young animals. Our recent findings which tend to challenge that framework are: 1) a blastema-based type of regeneration is a generic property of repair in excisional wounds in mouse ears, and 2) middle-aged mice of common strains are better regenerators than young post-weaning mice. However, viewed from a deeper biological perspective, our findings tend to corroborate the accepted view. Very simple and very young animals share the common attribute of incomplete histological differentiation. And mouse ears of very young and old mice share the common property of an exceptionally undifferentiated appearance. The mouse ear pinna contains no true differentiated cartilage, and is composed of large adipocyte-like chondrocytes known as "cellular cartilage" which has been likened to the cells of invertebrates and even plants. As mouse ear connective tissues derive from embryonic neural crest, we believe that neural-crest-derived connective tissues in mammals may never fully and truly differentiate and, for that reason, possess inherently greater regenerative capacity than similar tissues derived from other embryonic germ layers.