AJR 2013; 201:W919 0361–803X/13/2016–W919 © American Roentgen Ray Society Molecular Imaging Enhances Diagnostic and Management Targets in Patients With Cancer of Unknown Primary Site We read with great interest the article by Kim et al. [1] in the March 2013 issue of the American Journal of Radiology. The authors reviewed the role of imaging in the diagnosis and management of patients with cancer of unknown primary site (CUP). Within the current context of personalized medicine and targeted therapy, functional imaging should be considered as part of the approach to oncologic patients. We write to emphasize the importance of the study by Kim et al. and comment on the relevance of molecular imaging and target lesion detection in CUP. In recent decades, knowledge acquired about cellular and molecular mechanisms has improved our understanding of biologic behavior and tumor development. Simultaneously, new types of drugs have been developed that act directly on these mechanisms, known as targeted therapy [2]. Moreover, cancer is an extremely complex disease requiring multidisciplinary involvement. Imaging evaluation focused only on anatomic abnormalities can lead to misdiagnosis in several situations, such as silent disease and systemic inflammatory conditions and in patients with complex drug interactions. Such misinterpretation directly affects the selection of an appropriate approach, which may result in delayed or nonbeneficial treatment. Furthermore, the development of molecular imaging techniques that enable the assessment of metabolic activity, especially FDG PET/CT, MRI, and contrast-enhanced CT, represents a new paradigm in the evaluation of patients with CUP. Published data have proven that functional and anatomic joint evaluation improves the overall characterization, staging, response evaluation, and followup performance in patients with CUP [3]. The ability to recognize sites with areas of abnormal cellularity-metabolic activity using these tools usually enables specific diagnosis and provides essential information about molecular characteristics and biomarkers for selection of the best targeted therapy [2]. In many situations, such assessments have had significant impacts on the management of patients with cancer, improving quality of life and survival rates, especially in patients with advanced disease and those with CUP. Notwithstanding, diffusion-weighted MRI has been considered an alternative method for whole-body evaluation in cancer patients, including detection of the primary site of malignant disease [4]. Advantages of this modality include the avoidance of ionizing radiation exposure, excellent spatial resolution, and ability to collect information from different planes, which enable better characterization of several types of lesions, especially those in the bone, soft tissue, liver, and brain. Within the current context of targeted therapy, the use of modern diagnostic tools, including molecular imaging methods such as PET/CT and whole-body MRI, is essential in patients with CUP. These techniques optimize the diagnostic yields and enable selection of the most appropriate treatment, thus providing better management for these patients. Marcos Duarte Guimaraes Rubens Chojniak Hospital AC Camargo, Sao Paulo, Brazil Edson Marchiori Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil