Sjögren’s Disease (SjD) presents a challenge as a chronic, progressive, and systemic autoimmune disorder affecting approximately 0.05% of the population. SjD primarily targets exocrine glands, leading to severe dryness of the mouth and eyes, but can impact multiple organs and increase lymphoma risk. Despite advances in B cell-targeted therapies, no cure exists, and treatment remains symptom-focused, highlighting gaps in our understanding of SjD inflammatory environment. One roadblock to study the heterogeneity of the landscape in affected salivary glands in humans is the limited amount of tissue that is typically available from biopsies of minor salivary glands (MSGs). Spatial transcriptomics has emerged as a cutting-edge approach to address this challenge by preserving tissue architecture and enabling precise mapping of immune and structural cell interactions. This chapter explores how the Visium HD protocol from 10X Genomics can be leveraged to dissect the cellular and molecular landscape of formalin-fixed paraffin-embedded human MSGs, uncovering insights into disease mechanisms and therapeutic opportunities.