Time-of-Flight (TOF) Secondary Ion Mass Spectrometry started to be applied to biological cells as a chemometric methodology to study the cellular surface composition and the discriminations between normal and neoplastic cells, an issue that can be challenging in cases where neoplastic morphological features may not be evident, such as low grade prostate cancer and bladder cancer [53,54], or to study the chemical composition that can differentiate subtypes of well-defined neoplasia, such as estrogen-receptor-positive (ER+) and estrogen-receptor-negative (ER−) breast cancers [55]. This evidence concerns the gene ESR1 and urinary bladder cancer.