Critical to generating robust single cell or tissue gene expression data is ensuring that the source samples are procured and processed in a way that minimizes artifacts. This is especially critical for generating single cell/nucleus gene expression data from adult human tissue samples that are difficult to dissociate and might require prolonged manipulations that will introduce stress response signatures. We describe methods to: minimize these unwanted processing effects to enable interrogation of limited tissues, such as biopsies; allow histological validation and quality assurance and control of the samples; ensure compatibility with both single cell assays and orthogonal technologies. This involves preparing fresh frozen O.C.T. embedded tissue cryoblocks to collect thick sections for gene expression studies and adjacent sections for QA/QC, bulk RNAseq, DNA preparation or multiplex in situ RNA hybridization. The protocol for embedding limited amount of tissue for cryosections and susequent OMICS studies should be applicable to several solid organs and biopsies.