A sensitive, accurate, and simple method, called shifted termination assay (STA), was developed for detection of genetic mutations. The STA technology can be used to detect genetic mutations in polymerase chain reaction (PCR)-amplified samples of tissue, and plasma and serum that include circulating DNA containing point mutations, insertions, deletions, translocations, or single nucleotide polymorphisms (SNPs). STA is a multiple-base and multiple-cycle primer extension based detection method that can identify mutant DNA in samples containing as little as 1% mutant DNA in a mixture with 99% wild-type DNA. On the basis of the STA method, a mutation detection kit, called Mutector, was developed. Mutector is a 96-well microplate format test kit with colorimetric or luminescent detection options. An initial study shows that Mutector is more accurate and sensitive than sequencing and PCR restriction enzyme analysis methods in detecting DNA mutations from clinical samples.