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Background: Lemierre’s syndrome (LS), previously termed the “forgotten disease” after the introduction of modern antibiotics, is a rare and potentially fatal infection of the neck resulting in septic thrombophlebitis of the internal jugular and other neck veins. In recent years, there has been an increased resurgence of this disease, or at least in its detection, and it remains an important diagnosis with life-threatening potential to consider when presenting with multifocal cavitary pneumonia. Fusobacterium necrophorum, an obligate anaerobic Gram-negative bacterium, is the most isolated culprit organism involved in this condition; however, it is often fastidious and difficult to culture. The use of 16s rRNA gene sequencing can aid in this diagnosis when uncertainty exists. Methods: This case report describes an otherwise healthy 17-year-old male with a history of regular vaping presenting with upper respiratory infectious symptoms who was ultimately diagnosed with multifocal necrotizing pneumonia. In this case, there was initial diagnostic uncertainty as traditional microbiologic culture mechanisms failed to identify a causative organism for tailored antimicrobial treatment. This was despite direct empyema fluid analysis and pulmonary-bronchial biopsy. Novel gene sequencing was performed using 16s rRNA typing, a promising new way to identify a catalog of host organisms, detecting F. necrophorum. This diagnosis prompted further diagnostic imaging of the neck, confirming a small internal jugular clot and diagnosis of LS. Results: This case highlights the need for suspicion of LS in patients presenting with multifocal pneumonia. Furthermore, it re-iterates the idea of culture-negative infections, whereby fastidious organisms or tissue samples do not readily provide a diagnosis. Lastly, it further introduces hypotheses regarding the use of vaping as a possible associated factor for significant infection and lung injury. Conclusions: The use of 16s rRNA sequencing for the detection of fastidious, opportunistic organisms is another tool for physicians to ensure additional diagnostic clarity and appropriate treatment.