Mayo Clinic Laboratories > Cytology: A compelling molecular testing approach

Cytology: A compelling MOLECULAR testing approach

Achieve answers for more patients

The use of cytology specimens for molecular analysis of solid tumors is a proven means to establish a patient’s molecular diagnosis — a vitally important aspect of choosing the most effective treatment for a patient’s specific cancer. When the amount of available tissue specimen is inadequate for molecular testing, use of cytology specimens presents a compelling testing approach.

Cytology specimen testing, however, is considerably underutilized. In fact, recent Mayo Clinic Laboratories research into the use of cytology testing showed that cytology samples comprise just 18% of specimens submitted for comprehensive genomic profiling to detect somatic alterations in solid tumors.1 Among the reasons for this underuse are lack of validation of molecular tests for cytology samples and fear of sample inaccessibility following testing.


of comprehensive solid tumor cases ordered by Mayo Clinic physicians used cytology


of comprehensive solid tumor cases ordered by external clients used cytology

Learn more about the benefits of cytology testing directly from Mayo Clinic physicians, molecular pathologists, and laboratory scientists.
Mayo Clinic Laboratories research has shown testing equivalency between cytology samples and formalin-fixed paraffin-embedded (FFPE) tissue samples submitted for comprehensive, next-generation solid tumor sequencing.
Ensuring molecular adequacy of specimens begins with the collection process. At Mayo Clinic, rapid onsite evaluation and slide review helps ensure sufficient tumor cells have been collected for molecular analysis.

Transforming cancer testing

To help providers overcome any hesitancy toward using cytology samples for molecular testing and minimize instances of tumor inadequacy due to insufficient tissue samples, we’ve produced an educational resource backed by Mayo Clinic cytology testing experts.

Our digital guide is a must-read for providers looking to gain precision answers and personalize treatment for their patients.

Fill out the form to download our e-book

Ensuring Desired Molecular Testing Results for Cancer Patients, Cytology Specimen Utilization: A Proven Approach to Genetic Sequencing

“The availability of robustly validated NGS testing on cytology specimens ensures that more oncology patients get the successful NGS testing that is so critically important for guiding their care.

Kevin Halling, M.D., Ph.D., co-director of the Genetics and Genomics Laboratory

An advantageous alternative

The use of cytology samples for molecular testing has several advantages. The cellular integrity of smear specimens, which are typically prepared with alcohol-based fixatives, is often superior to FFPE tissue specimens. And unlike FFPE tissue block preparations, which entail cutting the block and the embedded cells within, direct smear cytology slides are prepared by applying whole cells directly onto the slide. This preserves the structure of the cells’ genetic contents.

More importantly, especially for lung and liver tumors, cytology specimens are sometimes the only type of specimen available for testing. In other cases, biopsied FFPE tissue samples are entirely or almost entirely needed for histopathological or immunohistochemistry testing, leaving insufficient material for molecular investigations.

We recognize that when cytology specimens are submitted alongside FFPE tissue samples, a high molecular testing success rate can be attained. We have validated nearly all our NGS oncology panels to accept cytology specimens, including smears and cell blocks.


  1. Knight S, Pitel B, Peterson B, et al. Cytology Specimens Perform Equivalently to FFPE Specimens and Are Underutilized for Somatic Comprehensive Genomic Profiling. Poster presented at: 112th United States and Canadian Academy of Pathology Annual Meeting; March 11-16, 2023; New Orleans, Louisiana.
(BETA) Choose a language to view this content in:
About the translation.