Brain biopsies and cerebrospinal fluid collection are frequently used in neuroscience research and require precise execution. The objective of this chapter was to provide updated protocols for brain biopsies and other stereotactic procedures in adult mice. The described technique employing a stereotactic arm enables greater precision than freehand techniques. Stereotactic procedures in adult mice can be performed expeditiously and demonstrate high efficacy in reaching the target site. Efficacy is contingent upon the complexity of precisely targeting the biopsy site, owing to the diminutive size of the animal. This chapter describes an innovative, efficient, and reproducible surgical protocol for brain biopsy and cerebrospinal fluid collection in adult mice.