We report on a case of cervical adenocarcinoma in situ in a 42-year-old woman with a history of human papillomavirus infection. Repeat cytology, human papillomavirus testing, and colposcopy failed to identify the lesion. Testing of the cervical cell DNA identified chromosomal abnormalities, prompting a cervical cone biopsy, which identified adenocarcinoma in situ. (Arch Pathol Lab Med. 2013;137:1829-1831 doi: 10.5858/arpa.2012-0499-CR) REPORT OF A CASE A 42-year-old woman, gravida 1, para 1, visited her new gynecologist for routine gynecologic care. Papanicolaou testing performed at her visit revealed atypical squamous cellsunknown significance with rare atypical cells. Reflex human papillomavirus (HPV) testing findings were positive for high-risk subtypes. The patient indicated her previous Papanicolaou tests had been normal. A decision was made to do a follow-up Papanicolaou test in 6 months because of the provided clinical history and because only rare atypical cells were seen on this Papanicolaou test.At the 6-month follow-up, Papanicolaou testing revealed atypical endocervical cells, not otherwise specified. Because of a repeat abnormal Papanicolaou result and a history of testing positive for HPV, the patient was scheduled for colposcopy and endocervical curettage. Multiple biopsies (8) of the transformation zone and acetowhite epithelium were taken during an adequate colposcopy procedure. Pathology revealed cervical intraepithelial neoplasia (CIN) 1, and endocervical curettage showed squamous metaplasia. This was done in accordance with American Congress of Obstetricians and Gynecologists (ACOG) and American Society for Colposcopy and Cervical Pathology (ASCCP) guidelines.A Cervical DNA Dtex test (NeoDiagnostix, Rockville, Maryland) for chromosomal abnormalities was performed on the second Papanicolaou specimen because of the lack of correlation between histology and cytology. This test showed significant DNA damage, with 13% of the cells being abnormal (Figure). DNA damage at 3q26 and 5p15 is associated with cervical carcinogenesis.1-4 The threshold value for a negative Dtex result is the presence of less than 1% abnormal cells. The 2006 ASCCP guidelines suggest 3 possible options for the management of a patient with an Atypical Glandular Cells Papanicolaou test with colposcopic biopsy showing CIN 1 and a negative endocervical curettage: (1) excisional procedure; (2) review of all findings; or (3) follow-up with subsequent Papanicolaou and colposcopy in 6 months. With the advantage of the additional information provided by the Cervical DNA Dtex test, the clinician chose (1), the first option. The physician decided to do a cold knife conization to rule out a more severe lesion. The cone biopsy, excised to a depth of 2.8 cm, revealed adenocarcinoma in situ (AIS) without squamous lesions. The pathology report also commented that the tissue test result was strongly positive for p16 and Ki-67, which are shown to be markedly elevated with AIS.5 As per gynecologic oncologist recommendation, the patient unde...