Few institutions have shaped neuropathology as a discipline as profoundly as Massachusetts General Hospital (MGH) and Harvard Medical School. Their fascination over many decades is due to a unique accumulation of excellent, intellectually stimulating neurologists with a sincere interest in the morphologic and pathogenetic basis of nervous system diseases. Their approach was strictly case oriented and clinico-pathological conferences were developed to the highest standard. In this review, the foundations of neuropathology in Boston are recounted.