Molecular imaging comprises a series of diagnostic modalities that provide information on the physiology and molecular composition of cells and tissues. One of these modalities, radioimmunodetection, uses radiolabeled monoclonal antibodies (mAbs) to image tissues. Two radioimmunodetection modalities are described in this article: immunoscintigraphy and radioimmunoguided surgery (RIGS). In immunoscintigraphy, the radioactivity is measured with the use of an external gamma camera and used to create images. In RIGS, the radioactivity is detected intraoperatively with the use of a handheld gamma probe to help the surgeon detect foci of otherwise occult disease. Both techniques have the potential to improve the preoperative and intraoperative localization of cancer. Multiple studies have been performed on the efficacy of RIGS on different malignancies, especially colorectal cancer. Despite the good sensitivity of the technique, some concerns revolve around the high rate of false positives and the real significance of leaving RIGS-positive tissue behind in terms of long-term outcomes and survival. More studies are warranted to further develop the technique and determine the specific role it will play on the diagnosis and management of surgical disease. Surgeons should actively participate in these studies and in expanding the applications of this promising technology.