Objectives: Recently, there have been important advances in the clinical application of targeted hybrid near-infrared (NIR) fluorescent-radioactive tracers. ICG-99mTc-nanocolloid, for example, is already being used by some centres for sentinel lymph node biopsy in head and neck cancer. The radioactive component allows imaging at depths which would not be possible with NIR alone and, once exposed, the NIR fluorescence reporter can be imaged at very high resolution. Gamma detection is currently carried out with a separate hand-held gamma camera or with a non-imaging probe. Visualisation of NIR fluorescence during surgery requires a dedicated NIR camera, several of which are available commercially. We describe a novel hand-held hybrid NIR-gamma small field of view camera, capable of displaying co-aligned images from both modalities, which can be fused into one image or viewed separately. This study is a preliminary investigation of the performance of the fluorescence component of this camera, including phantom studies and first images from a preclinical pilot study. Methods: The hybrid camera consists of a 1500 µm thick thallium doped caesium iodide columnar (CsI:Tl) scintillator coupled to an electron multiplying charged coupled device (EMCCD). A 1.0mm diameter tungsten pinhole collimator gives a 40mm x 40mm nominal field of view for an 8mm x 8mm CCD detection area. A fluorescence camera was aligned to provide the same field of view as the gamma camera with an LED ring as the excitation source. The performance of the fluorescence imaging was quantified in this study for the fluorophores ICG and IRDye800CW (CW800) using a range of bespoke phantom experiments. In vivo images were also obtained from a preclinical study of a targeted hybrid tracer (cRGD-CW800-TCO + TCO-DOTA-111In) in mice with HT29 colorectal cancer xenografts. RESULTS AND CONCLUSION: The portable hybrid camera prototype has been shown to successfully image dual NIR-gamma tracers using both in vitro and in vivo experimental models. With further development, this camera could be used intraoperatively, offering the benefits of gamma imaging at depth in tissues and high resolution surface NIR fluorescence imaging in a single imaging system.