Functional differences among human cells have been difficult to identify by standard biochemical methods. Loss-of-function shRNA screens provide an unbiased method to compare protein requirements across cell lines. In previous work, we have studied kinase requirements in two settings, either among a panel of cells from numerous tissues or between two cell lines that differ only by the expression of a chosen oncoprotein or tumor suppressor protein. Here we examine the patterns of kinase requirements between two unrelated cells, the cervical carcinoma cell line HeLa and the renal carcinoma cell line 786-O. By using time courses of cell proliferation after shRNA transduction and by introducing different levels of the shRNAs, we were able to carefully compare the kinase requirements. These comparisons identified 10 kinases that were required in HeLa but not 786-O, and 5 kinases that were required in 786-O but not HeLa. The patterns of growth inhibition due to particular sets of shRNAs in a tumor cell line were shown to be similar in some but not all cell lines derived from the same tissue-specific cancer type. Differential kinase requirements promise to be useful in distinguishing important cell-to-cell functional variations and may lead to the identification of fingerprints for different physiological cell states.