We introduce a new approach that enables Surveyor TM to scan for mutations over one or several PCR products simultaneously and selectively amplify and isolate the mutation-containing DNA fragment(s) via linkermediated PCR. By selectively amplifying mutationcontaining DNA from wild-type fragments, the present approach de-couples enzymatic mutation scanning from the endpoint detection step. As a result, following enzymatic action on mismatches any chosen DNA detection method (real-time PCR, gel/capillary electrophoresis, microarray-based detection) can potentially be used to identify the mutated DNA fragments in a simplex or multiplex fashion. Here we utilize real-time PCR coupled with melting curve analysis (Surveyor TMmediated Real Time Melting, s-RT-MELT) to validate the new technology. We demonstrate that this approach increases the mutation scanning throughput by 1-2 orders of magnitude when several (4100) samples are to be pre-scanned for mutations, enables mutation scanning over several PCR fragments simultaneously and mutationpositive samples can be directly sequenced when somatic mutations are at a low-level ($1-10% mutantto-wild-type ratio) in surgical cancer specimens.