A 2-year-old female guinea pig was referred for management of a urethral stone. The stone was diagnosed on radiographs following a 10-day history of stranguria, dysuria, and hematuria. Attempts to remove the stone by urethral catheterization and flushing were unsuccessful. The stone was successfully fragmented and removed by cystoscopic-guided transurethral laser lithotripsy, performed under general anesthesia. The postoperative recovery was uneventful, and hematuria and stranguria resolved 24 hours after the procedure. The animal presented a good urine stream immediately following the procedure and continued to urinate well at recheck a month later. This is the first report of transurethral laser lithotripsy for the treatment of a partially obstructive urethral stone in a guinea pig. This minimally invasive approach provided excellent visualization of the urethra and bladder and allowed complete evaluation of the lower urinary tract in a retrograde manner in this female guinea pig. This novel approach holds great promise for the future treatment of lower urinary tract stones in this species.