Abstract Histological analysis of animal and human tissues has played a key role in our understanding of development, homeostasis, and disease in the musculoskeletal system. Fundamental histologic approaches and techniques remain important tools for cutting-edge research projects. Additionally, the last few years have seen the development of new methods for molecular analyses performed in situ, including spatial transcriptomics and multiplex immunofluorescence. The complex cellular composition and location-dependent function of cells in the skeleton make these approaches particularly attractive to researchers. However, the unique nature of musculoskeletal tissues (e.g. calcification, unique and abundant extracellular matrix, large differences in composition of adjacent relevant structures, etc.) renders them a substantial technical challenge. The presence of high-quality core services enables investigators to incorporate these state-of-the-art analyses, along with standard but expertly performed techniques, into their research programs without hiring lab staff with histology experience. Our comprehensive approach promotes appropriate qualitative and quantitative assessment of musculoskeletal histology while facilitating the rigor and reproducibility of core-associated results. We continually adapt to the needs of our Research Community by meeting with investigators to assess their needs and to provide individualized service. We also continue to work with the Washington University Center for Cellular Imaging (WUCCI), a well-equipped microscopy resource on campus, to provide state-of- the-art imaging options for downstream analysis of sections produced by our Core. Aim 1 – Histology services: 1) Processing, embedding, and sectioning utilizing paraffin, MMA/plastic, and frozen section approaches, performed by Core staff; 2) 20+ routine and special stains performed in the Core; 3) Access and support for trained users. Aim 2– Resources for Imaging and Analysis: 1) Local, in-core confocal microscope; 2) In-core BioQuant Osteo system for histomorphometry; 3) Coordination with the Washington University Center for Cellular Imaging. Aim 3 – Consultation, training, and development/implementation of new techniques: 1) Individual consultation for project planning and data interpretation by Core staff and/or directors; 2) Individualized technical training for Core equipment; 3) Technical development and support for spatial molecular techniques; 4) Seminars and workshops. Aim 4 – Quality control and communication: 1) Support rigor and reproducibility; and with Core A 2) Maintain website with information on services, protocols, and didactic materials; 3) Communicate regularly with users about available services and other related resources, and survey needs.