TheBRAF V600Emutation in papillary thyroid carcinoma is the major mutation in classical subtype of papillary thyroid carcinoma and other cancers.Itis the most studied predictor of clinical and pathological characteristics as well as molecular targets for cancer therapy. On the other hand, there is potential for many more forms of activating mutation in BRAF that are not detectable by simple assays to detect V600E, or even simple polymerase chain reaction (PCR)-based sequencing for full-length BRAF. Such activating mutations could arise from larger-scale rearrangements which may apparently leave no sequence change to BRAF while causing increased expression or activation by unusual means, such as gene fusion. Detection of these kinds of changes can take place using a variety of methods, though capture-based sequencing can identify the existence of such forms of mutant BRAF without needing foreknowledge of the loci involved in these kinds of mutation. In this chapter, we detail a method for capture of specific DNA sequences and their amplification to prepare for massively parallel sequencing.