Apolipoprotein E (APOE) genotyping of genomic DNA extracted from formaldehyde-fixed specimens is cumbersome: there is not only a low yield or failure of PCR amplification (presumably due to degradation of DNA in the formaldehyde-fixed and paraffin-embedded tissue), but the standard method also involves the separation of DNA fragments as small as 48, 72, 81 and 91 bp requiring high-yield PCR products. Here we report about a semi-nested PCR method suitable for providing specific high-yield PCR products from DNA that has been extracted from formaldehyde-fixed specimens which initially generate low-quality templates. This method facilitates reliable APOE genotyping of DNA from difficult templates.