Gene set testing is a general method for relating gene expression studies across different experiments and technologies. When combined with information about the direction and strength of gene expression changes, a gene set can be used as a general representation of an expression signature that can fingerprint a cell type or biological process. Our laboratory uses rotation gene set tests as a flexible and rigorous technology for focused gene set tests and for expression signature analyses. This talk will describe some recent stories, including the use of transcriptional profiles to identify the likely cell of origin for squamous lung cancer.