Abstract Objective Data on breast imaging in symptomatic pregnant women are limited. Our aim was to assess the value of targeted breast US for the primary evaluation of breast symptoms in pregnant women of all ages. Methods This IRB-approved retrospective study included all pregnant patients who underwent targeted US for focal breast symptoms at an academic imaging facility over an 18-year period (2000–2018). Clinical, imaging, and pathology results were reviewed. Malignant outcomes were determined by histology. Benign outcomes were confirmed by pathology or ≥2 years of follow-up. Descriptive statistics and 2 × 2 contingency table analyses were performed at the presentation level. Results The study cohort comprised 178 presentations in 175 pregnant women. Mean age was 34.7 years (standard deviation, 5.2). The majority (153/178, 86.0%) were more than 30 years old. At presentation, 42.1% (75/178) were in the first trimester of pregnancy, 27.0% (48/178) in the second, and 29.8% (53/178) in the third. The most common presenting symptom was a palpable lump (162/178, 91.0%), followed by focal pain (7/178, 3.9%). The vast majority (174/178, 97.8%) of cases were non-malignant. However, targeted US detected all 4 malignancies (cancer detection rate, 22/1000; negative predictive value 136/136, 100%). Sensitivity and specificity were 100% (4/4) and 78.2% (136/174), respectively. Conclusion Benign causes of symptoms in pregnant women were far more common; malignancy was rare, accounting for only 2.2% (4/178) of cases. Targeted breast US detected all malignancies, supporting US as the primary imaging modality for evaluating symptomatic pregnant women, regardless of age.