Accurate tumor identification is essential in the management of cancer patients. For many types of cancer, surgical resection is the best or only chance for cure. Incomplete excision of tumor tissue however, negatively affects the prognosis of the patient. In many cases, the presence of (microscopic) residual tumor tissue at the resection margins is a direct predictor of patient survival. The completeness of tumor removal during surgery is dependent on the surgeon’s ability to differentiate tumor from normal tissue. Ideally, surgeons could use real-time information to detect tumors or positive resection margins during surgery. For this purpose intraoperative visualization techniques are commonly applied in different types of cancer. To accomplish radical excision of tumor tissue, radiotracers can be used that target tumor tissue and can be detected using a gamma probe during surgery. Yet, this technique cannot provide a precise delineation of the tumor and resection margins. The addition of a fluorescent label could help to overcome this limitation. Intraoperative fluorescence imaging could allow accurate real-time tumor delineation, but the penetration depth of emitted light in biological tissue is limited. So, a powerful synergy can be achieved by combining radiotracers for the detection of tumor tissue, and optical tracers for subsequent accurate delineation of tumors. We have shown the potential of this targeted dual-modality approach for intraoperative detection of tumor lesions in preclinical studies. Currently, we are implementing this in the clinic.