Early detection of structural or functional changes in dysplastic epithelia may be crucial for improving long-term patient care. Recent work has explored myriad non-invasive or minimally invasive "optical biopsy" techniques for diagnosing early dysplasia, such as high-resolution microendoscopy, a method to resolve sub-cellular features of apical epithelia, as well as broadband sub-diffuse reflectance spectroscopy, a method that evaluates bulk health of a small volume of tissue. We present a multimodal fiber-based microendoscopy technique that combines highresolution microendoscopy, broadband (450-750 nm) sub-diffuse reflectance spectroscopy (sDRS) at two discrete source-detector separations (374 and 730 μm), and sub-diffuse reflectance intensity mapping (sDRIM) using a 635 nm laser. Spatial resolution, magnification, field-of-view, and sampling frequency were determined. Additionally, the ability of the sDRS modality to extract optical properties over a range of depths is reported. Following this, proof-of-concept experiments were performed on tissuesimulating phantoms made with poly(dimethysiloxane) as a substrate material with cultured MDA-MB-468 cells. Then, all modalities were demonstrated on a human melanocytic nevus from a healthy volunteer and on resected colonic tissue from a murine model. Qualitative in vivo image data is correlated with reduced scattering and absorption coefficients. References and links 1. P. Sharma and E. Montgomery, "Gastrointestinal dysplasia," Pathology 45(3), 273-285 (2013). 2. P. M. Speight, "Update on oral epithelial dysplasia and progression to cancer," Head Neck Pathol. 1(1), 61-66 (2007). 3. Y. Zhang, "Epidemiology of esophageal cancer," World J. Gastroenterol. 19(34), 5598-5606 (2013). 4. N. Harpaz and A. D. Polydorides, "Colorectal dysplasia in chronic inflammatory bowel disease: pathology, clinical implications, and pathogenesis," Arch. Pathol. Lab. Med. 134(6), 876-895 (2010). 5. M. Ponz de Leon and C. Di Gregorio, "Pathology of colorectal cancer," Dig. Liver Dis. 33(4), 372-388 (2001). 6. M. J. Arends, C. H. Buckley, and M. Wells, "Aetiology, pathogenesis, and pathology of cervical neoplasia," J.Clin. Pathol. 51(2), 96-103 (1998 170-173 (2005). 11. M. Gu, H. Bao, and H. Kang, "Fibre-optical microendoscopy," J. Microsc. 254(1), 13-18 (2014) properties of pigmented skin lesions including melanoma using oblique incidence diffuse reflectance spectrometry," J.