<p>One of the most devastating central nervous system infections, progressive multifocal leukoencephalopathy (PML), is caused by the JC virus (JCV). In immunosuppressed patients, PML is a well-recognized complication recognized by clinicians across specialties, such as neurology, internal medicine, oncology, and rheumatology. It can be encountered in patients receiving hematopoietic or solid-organ transplants, cytotoxic chemotherapy, immune checkpoint inhibitors, or long-term immunosuppressive therapies. In neurological settings, those treated with natalizumab, rituximab, ocrelizumab, fingolimod, or dimethyl fumarate can be at risk of developing PML. The gold standard for diagnosing PML is the detection of JCV DNA in cerebrospinal fluid (CSF) by PCR in the context of compatible clinical and MRI findings. In cases where JCV PCR assay results are negative or inconclusive, the diagnosis may rely on brain biopsy or clinical/radiographic findings. However, an under-recognized vulnerability exists in the way JCV PCR results are reported—‘positive or negative’. The results omit critical assay metrics, such as the limit of quantitation (LOQ) and limit of detection (LOD) data. Hence, a false sense of diagnostic certainty prevails, leading to missed or delayed diagnoses of early stage PML, where viral loads are often low. Unless clinicians are aware of this possibility, a diagnosis of PML can be delayed or missed. This systemic reporting failure is a diagnostic shortcoming with consequences not just for patient care but is a potential legal minefield. Mandatory inclusion of LOQ and LOD across JCV PCR reports in CSF will provide diagnostic transparency and provide critical information that clinicians need.</p>