Since its inception more than 50 years ago at Memorial Hospital for Cancer (New York), needle aspiration biopsy has traveled to its present popularity over a torturous road. The early influence of Stewart on the interpretation of aspiration smears and the use of this biopsy method is still worthy of review, particularly the importance of close cooperation between clinician and pathologist. While cytology has been profoundly influenced by individual cell interpretation as practiced by Papanicolaou, it is really pattern recognition that dominates successful diagnosis by the aspiration biopsy smear method. Present concerns over technical variation in procurement of the biopsy and staining methods should be of less importance than identification of the aspiration methodology that produces the best-quality microscopic image. Reliability of diagnosis by aspiration smear must also be judged by a suitable and reproducible standard, something that is not necessarily fulfilled by tissue pathology, although many would believe otherwise. The author proposes that aspiration may also now be judged, like tissue pathology, by clinical outcome. The application and ease of procuring cell samples from tumors for cell image analysis, for flow cytometry and ploidy studies, and for gene rearrangement place this biopsy method in the forefront of the integration of biologic research and clinical medicine. Aspiration biopsy has caused us to explore how the human eye and brain analyze microscopic images and may even assist in the design of useful artificial intelligence diagnostic systems in the future.