Objective: To investigate the feasibility of the first trimester (FT) ultrasound scan (US) for the evaluation of the fetal portal venous system (PVS) anatomy, and to evaluate the potential of microcopy for a proper pathology evaluation for the PVS in the FT. Methods: We evaluated the PVS in 200 scan examinations performed in FT pregnancy. Half of the cases were scanned by two operators with extensive experience in obstetric ultrasound—Group I, and the other half was evaluated by two sonographers with less experience—Group II. Second-trimester US and autopsy in terminated pregnancies were used as follow-up. The pathologic evaluation was supported by microscopy. Results: all PVS features were successfully assessed by transabdominal ultrasound (TAUS) in 27% of the Group I cases and 14% in Group II. These rates increased to 88% in Group I and in 72% in Group II, after rescanning and using transvaginal ultrasound (TVUS). The conditions that led to rescanning and TVUS were: BMI greater than 24 in 26% cases, unfavorable fetal position (12.32%), retroverted uterus (12.32%), abdominal scar (10.96%), fibroids (4.11%), and combinations of the above (34.23%). The L-shaped UV confluence was identified transabdominally in 91% in Group I and in 79% in Group II and increased to 98% and 95%, respectively, following reevaluations. Microscopy represented a useful audit in all FT investigated cases. Conclusions: At the end of the FT, the visualization of a normal L-shaped UV confluence, that excludes major PVS abnormalities, is achievable in approx. 80%, indifferently the examiners experience. The sonographers experience, pregnant women BMI, and uterine anomalies as fibroids or retroversion significantly affect the rate of visualization, and necessitates vaginal approach and reexamination. The FT pathology, the audit of the ultrasound findings can only be performed microscopically, with relatively little resources involved and good results.