The concept of the biopsy is ubiquitous in current medical diagnosis of cancer and other diseases. The standard biopsy consists of removing a sample of tissue for evaluation and diagnosis, primarily to ascertain the presence of cancer cells by (histo)pathological analyses. However, the advent of new optical imaging modalities and targeted or "smart" agents, that have affinity for a select target, suggests the possibility of performing in vivo tissue characterization without the need for sample removal or the wait for histopathologic processing. Here we present work testing and validating a fiber-based confocal fluorescence microscopic imaging system intended for combination with a larger scale imaging modality (i.e. MRI or CT) to be used in image-guided in vivo tissue characterization. Fiber-based confocal fluorescence microscopic imaging experiments were performed (Cellvizio, Mauna Kea Technologies, Paris, France) in vivo in two mouse models including: 1) EGFP-expressing mouse melanoma model and 2) M21 mouse melanoma model. Both models are known to express integrin αvβ3, a cell-surface receptor protein. We also performed an experiment in ex vivo chicken muscle tissue labelled with a fluorescein isothiocyanate-lectin targeted compound. In the mouse models, contrast agents that targeted the integrin were injected and the contrast agent localization in tumor was verified by a whole-body multispectral imager. The fiber-based tool was sensitive enough to detect and image the tissue of interest in all different experiments, and was found appropriate for use in interventional catheter-based procedures.