Tubulin, the cellular target for the taxane chemotherapeutic agents, is composed of heterodimers. There are at least six human genes encoding different tubulin subunits (1). In most epithelial tumor cells, the most highly expressed isoform of -tubulin is 5, which is encoded by the TUBB gene, also referred to as M40 (2). Chinese hamster ovary cells (3) and an ovarian tumor cell line (4) adapted for growth in vitro in the presence of the taxane paclitaxel have been found to have mutations in TUBB. Monzo et al. (5) reported TUBB mutations in 16 (33%) of 49 tumor samples from previously untreated patients with advanced non-small-cell lung cancer (NSCLC). All of the mutations, except two, were located in exon 4, which encodes more than half of the -tubulin protein and includes the adenosine triphosphate-binding site composed of the ribose-, phosphate-, and base-binding regions. There was also a statistically significant association between the presence of TUBB mutations and both poor treatment response to paclitaxel-containing chemotherapy and shortened overall survival (5). These associations led to the proposal to use the presence of TUBB mutations as a basis for selecting initial chemotherapy for patients with advanced NSCLC (6). To better study the association between TUBB mutations and tumor cell growth and taxane resistance in patients with NSCLC, we selected 25 tumor cell lines (supplementary Table 1, available at the Journal’s Web site http://jnci. oupjournals.org) that differed in their in vitro sensitivity to paclitaxel (7). Genomic DNA was isolated from these cell lines, from normal human peripheral blood leukocytes, and from 20 NSCLC primary tumor samples by proteinase K digestion and phenol–chloroform extraction. Patients providing a tumor sample gave written informed consent to use their tumor under an institutional review board-approved human study. Oligonucleotides for polymerase chain reaction (PCR) amplification of the coding regions of TUBB were designed on the basis of the genomic sequence of TUBB from the Human Genome Project (GenBank accession number AC006165) with the use of GeneWorks version 2.45 (IntelliGenetics, Mountain View, CA). At least one oligonucleotide was required to be within an intronic sequence. Oligonucleotides used in the amplification and sequencing reactions were as follows: Exon 1—1F, 5 -CCCATA-