Two families with positive histories of genetic diseases involving rapidly progressing dementia and various neurological syndromes are presented. Clinical symptoms and laboratory test outcomes in members of both families suggested family susceptibility to Creutzfeldt-Jakob's disease but were insufficiently pronounced to justify a diagnosis of "probable CJD". Later post mortem neuropathological examinations, together with monoclonal antibody responses led to diagnosis of Alzheimer's disease in the first family and spongiform encephalopathy in the second family. The final, complete diagnoses were only reached after genetic tests were conducted. These revealed: family AD with early onset and mutation in the preseniline 1 gene (codon 117 – Prol117Leu) and GSS syndrome with mutation in gene PrP (codon 102 – Prol102Leu). The significance of genetic and neuropathological tests for the diagnosis of family susceptibility to dementia diseases and atypical neurological symptoms is emphasized.